80% of Psoriasis due to CARD4 (NOD1) Gene Mutation -> PSORS2 -->> Anne Bowcock & CREW<<<------

[randall]

hi

What's in the cARDS today?

MY psoriasis CLEARs uP?

Well YeS and NO(D).

OK don't NOD off, but your psoriasis NOD1 gene is FUNKY.


WHAT?


REALLY? Really? really?


yes Yes YES....

And 80% of all psoriasis is due to CARD4, aka- NOD1.

Mutating OFF...

Yikes...

BTW, monkey's don't have bad NOD1 gene's. Only PSOR humans and most
likely
due to monkey business around the toba catastrophe time period?

http://en.wikipedia.org/wiki/Toba_catastrophe_theory#Genetic_bottlenecks_related_to_the_human_population

Or back during paleo times eating some bad cheese? Or plant? Or
to much D3 or not enough? Or a virus? Or bacteria? or er er er
erap1?

Scientist (for psoriasis and genes), Anne Bowcock et al found a
mutated CARD14 gene in PSORS2?


Don't have the pmid # yet,...do have their abstract from CELL


http://www.cell.com/AJHG/abstract/S0002-9297(12)00156-5
Anne Bowcock and Alan menter et al (will post the et al's when the
pmid comes out)

Abstract:
Psoriasis is a common, immune-mediated genetic disorder of the skin
and is associated with arthritis in approximately 30% of cases.
Previously, we localized PSORS2 (psoriasis susceptibility locus 2) to
chromosomal region 17q25.3-qter after a genome-wide linkage scan in a
family of European ancestry with multiple cases of psoriasis and
psoriatic arthritis. Linkage to PSORS2 was also observed in a
Taiwanese family with multiple psoriasis-affected members. In caspase
recruitment domain family, member 14 (CARD14), we identified unique
gain-of-function mutations that segregated with psoriasis by using
genomic capture and DNA sequencing. The mutations c.349G>A
(p.Gly117Ser) (in the family of European descent) and c.349+5G>A (in
the Taiwanese family) altered splicing between CARD14 exons 3 and 4. A
de novo CARD14 mutation, c.413A>C (p.Glu138Ala), was detected in a
child with sporadic, early-onset, generalized pustular psoriasis.
CARD14 activates nuclear factor kappa B (NF-kB), and compared with
wild-type CARD14, the p.Gly117Ser and p.Glu138Ala substitutions were
shown to lead to enhanced NF-kB activation and upregulation of a
subset of psoriasis-associated genes in keratinocytes. These genes
included chemokine (C-C motif) ligand 20 (CCL20) and interleukin 8
(IL8). CARD14 is localized mainly in the basal and suprabasal layers
of healthy skin epidermis, whereas in lesional psoriatic skin, it is
reduced in the basal layer and more diffusely upregulated in the
suprabasal layers of the epidermis. We propose that, after a
triggering event that can include epidermal injury, rare gain-of-
function mutations in CARD14 initiate a process that includes
inflammatory cell recruitment by keratinocytes. This perpetuates a
vicious cycle of epidermal inflammation and regeneration, a cycle
which is the hallmark of psoriasis.
<snip>


It's NOT like runx*--> Anne Bowcock, isn't on top of this ONE.


Five hits (out of 161) for: psors2 + Bowcock -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=psors2%20bowcock

160 hits-- "Bowcock AM"[Author]
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bowcock%20AM%22%5BAuthor%5D

42 of 160 have psoria* for ANNE
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bowcock%20AM%22%5BAuthor%5D%20psoria*

<<actually 43 of 161 when the cell abstract above is on pubmed soon?>>

Anne Bowcock has 141 hits in the psoriasis newsgroup: p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=bowcock&start=0&

And Anne has three abstracts for the RUNX gene in regards to
psoriasis.


OK the big NEWs for PSORs today:


http://www.doctortipster.com/9320-research-identifies-gene-responsible-for-psoriasis.html
OR
http://medicalxpress.com/news/2012-04-gene-linked-common-psoriasis.html
First gene linked to common form of psoriasis identified
April 19, 2012 in Genetics

------

http://s.ph-cdn.com/newman/gfx/news/hires/2012/firstgenelin.jpg
Scientists led by Washington University School of Medicine in St.
Louis have identified the first gene directly linked to the most
common form of psoriasis. Rare mutations in the CARD14 gene, when
activated by an environmental trigger, can lead to plaque psoriasis,
which accounts for 80 percent of all cases of the condition. Credit:
National Psoriasis Foundation

---------

Scientists led by Washington University School of Medicine in St.
Louis have identified the first gene directly linked to the most
common form of psoriasis, a chronic skin condition

The research shows that rare mutations in the CARD14 gene, when
activated by an environmental trigger, can lead to plaque psoriasis.
This type of psoriasis accounts for 80 percent of all cases and is
characterized by dry, raised, red patches covered with silvery scales
that can be itchy and painful.

The new findings also indicate that mutations in CARD14 can be
involved in the pustular form of psoriasis and in a debilitating
arthritis linked to the psoriasis. The discovery may lead to more
effective, targeted therapies for plaque psoriasis and other forms of
the disease.

The research is published May 4 in two separate papers in The American
Journal of Human Genetics.

"We have searched for almost two decades to find a single gene linked
to plaque psoriasis," says the senior author of both papers, Anne
Bowcock, PhD, professor of genetics. "Individually, the rare mutations
we have found likely confer a high risk for the disease, and we think
they will be important in the search to find new, more effective
treatments."

Although psoriasis has long been thought to be caused by an overactive
immune system, the genetic pathway uncovered by the scientists points
to defects in the skin as the main culprit of the condition and to
immune cells as secondary players.

Now, the researchers want to find out how common the altered pathway
is in the different types of psoriasis and in patients with psoriatic
arthritis. Their work suggests that in at least some patients with
different forms of psoriasis, this pathway is the same.

An estimated 7.5 million Americans have psoriasis, and about 30
percent of them develop psoriatic arthritis. Like other common
diseases, psoriasis runs in families and has been thought to have a
genetic component, but it's been difficult to pin down the genes
involved. That's because common variations in genes likely contribute
very little to the overall genetic risk of the disease, and mutations
that substantially increase a person's risk are so rare they have been
impossible to find.


With early support from the National Psoriasis Foundation, Bowcock
initiated the research with co-author Alan Menter, MD, of the
Psoriasis Research Institute at the Baylor College of Medicine.

Using the latest DNA technology to sequence all of a patient's genes,
Bowcock and her colleagues uncovered a rare CARD14 mutation in a large
family of northern European descent in which plaque psoriasis was
prevalent. They also found the mutation in the one-third of family
members who had developed psoriatic arthritis, suggesting that the
same rare mutation can play a role in both conditions.

The scientists also identified another rare CARD14 mutation in an
extended family from Taiwan that had a large number of plaque
psoriasis cases.

But mutations in the gene do not only occur in families with a genetic
predisposition.

The researchers, including the papers' first author Catherine Jordan,
an MD/PhD student at Washington University, also found a CARD14
mutation in a 3-year-old girl with a severe case of pustular
psoriasis, a rare form of psoriasis. Neither of the girls' parents had
mutations in CARD14, indicating that the rare mutation was not
inherited but had occurred spontaneously.

Psoriasis typically develops after an environmental trigger, which can
include an infection, such as strep throat, or injury to the skin,
including a cut or bug bite. Certain medications, smoking and heavy
alcohol consumption also are triggers.

The young girl, from Haiti, developed psoriasis in infancy, like some
members of the family with origins in northern Europe.

"This is significant because it tells us that CARD14 mutations alone
are enough to lead to psoriasis, possibly after an early trigger such
as an infection," Bowcock explains. "You don't need anything else.
This really highlights the importance of finding rare mutations for
common diseases like psoriasis."

The researchers also found 15 other rare mutations in CARD14. In a
finding that is statistically significant, the mutations were more
common in more than 6,000 patients with psoriasis compared to 4,000
healthy controls.

The scientists showed that in specialized skin cells called
keratinocytes, mutations in CARD14 increase the activity of NF-kappaB,
a protein that turns on genes. This protein increases the production
of certain signaling molecules that attract inflammatory cells to the
skin, unleashing a vicious cycle of inflammation that is so notable in
psoriasis.

Psoriasis affects the life cycle of skin cells, causing them to mature
rapidly in just a few days and accumulate to form thick, scaly
patches. Interestingly, in psoriasis patients with CARD14 mutations,
the researchers found the gene's activity was increased in the upper
layers of the skin, which may explain the flakiness that characterizes
the condition.

"Now, we have a much clearer picture of what is happening in
psoriasis," Bowcock says. "And with all kinds of new therapeutic
targets that lie within the CARD14 pathway, the field is wide open."

More information: The American Journal of Human Genetics. May 4, 2012.
http://www.cell.com/AJHG/
http://medschool.wustl.edu/
<snip>

7 hits for CARD4 - p ng (5 of those have nod1)
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=card4&start=0&

21 hits for nOD1 - p ng (5 with card4)
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=+nod1&start=0&scoring=d&


http://en.wikipedia.org/wiki/NOD1
Symbols NOD1; CARD4; CLR7.1; NLRC1
Nucleotide-binding oligomerization domain-containing protein 1 is a
protein receptor that in humans is encoded by the NOD1 gene.[1][2] It
recognizes bacterial molecules and stimulates an immune reaction.

NOD1 protein contains a caspase recruitment domain (CARD). NOD1 is a
member of NOD-like receptor protein family and is a close relative of
NOD2. NOD1 is an intracellular pattern recognition receptor, which is
similar in structure to resistant proteins of plants, and mediates
innate and acquired immunity by recognizing bacterial molecules
containing D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety. Nod1
interacts with RIPK2 through the CARDs of both molecules (See the
structure of the NOD1 CARD in the right panel). Stimulation of NOD1 by
iE-DAP containing molecules results in activation of the transcription
factor NF-κB.
<snip>

Card4 is NOD1:
http://www.ncbi.nlm.nih.gov/gene/10392
NOD1 nucleotide-binding oligomerization domain containing 1 [ Homo
sapiens ]

[...] This gene encodes a member of the NOD (nucleotide-binding
oligomerization domain) family. This member is a cytosolic protein. It
contains an N-terminal caspase recruitment domain (CARD), a centrally
located nucleotide-binding domain (NBD), and 10 tandem leucine-rich
repeats (LRRs) in its C terminus. The CARD is involved in apoptotic
signaling, LRRs participate in protein-protein interactions, and
mutations in the NBD may affect the process of oligomerization and
subsequent function of the LRR domain. This protein is an
intracellular pattern-recognition receptor (PRR) that initiates
inflammation in response to a subset of bacteria through the detection
of bacterial diaminopimelic acid. Multiple alternatively spliced
transcript variants differring in the 5' UTR have been described, but
the full-length nature of these variants has not been determined.
[provided by RefSeq, Oct 2009]
<snip>



OK so maybe LPS from endogenous endotoxin and STAPH are critical with
NOD1?

Is Card4/NOD1 mutation the trigger that runs 24/7 after strep or some
psor trigger?

So LOOK at this one: <has a nice jpg for ykw>

http://www.pasteur.fr/recherche/RAR/RAR2009/Cytoinf-en.html
Cytokines and inflammation - GDR CNRS 3048
Sensing and signalling in response to Staphylococcus aureus differ
between peritoneal macrophages, alveolar macrophages and monocytes

[...]Contribution of NOD2 in the sensing of S. aureus in vitro andin
vivo

[...]Biofilm-forming Pseudomonas aeruginosabacteria undergo LPS
structuralmodifications and induce enhanced TNF production in human
monocytes
<snip>

http://www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-departments/infection-and-epidemiology/units-and-groups/cytokines-e-inflammation/research-activities

Abstract
We study the early phase of innate immunity, namely, the mechanisms
involved in cytokine induction by Gram-negative or Gram-positive
bacteria and their pathogen-associated molecular patterns (PAMPs).
While this response is a prerequisite to fight infection, its
overwhelming activation may be associated with deleterious effects as
those seen during septic shock or non-infectious systemic inflammatory
response syndrome (SIRS). On another hand, the counteracting anti-
inflammatory response may lead to an altered immune status
(compensatory ant-inflammatory response syndrome, CARS). We study the
production of cytokines and their involvement in different
inflammatory disorders in humans (sepsis, trauma,
ischemia/reperfusion, cystic fibrosis). We investigate at the
intracellular signaling pathways level, the reprogrammation of
circulatory cells, reminiscent of the endotoxin tolerance henomenon,
that could be linked to the increased susceptibility of these patients
to nosocomial infections
<snip>

[...] http://www.pasteur.fr/ip/portal/action/WebdriveActionEvent/oid/01s-00001t-036
Toll-like receptors (TLR) are involved in the sensing of microbial-
derived compounds. Nod1 and Nod2 are intracytoplasmic sensors that
recognize distinct peptidoglycan-derived muropeptides. We analyzed the
contribution of these receptors to cytokine production by macrophages
following stimulation with whole bacteria. Using knockout mice, we
determined that TLR4 and TLR2 contribution was predominant in the
induction of TNF and IL-10 by Gram-negative bacteria. In contrast, the
absence of TLR2 and/or TLR4 or TLR9 did not affect the response to
Gram-positive bacteria. In the absence of TLR2, the phagocytic
property of macrophages was essential for cytokine production in
response to heat-killed Staphylococcus aureus (HKSA) and was markedly
inhibited by cytochalasin D. By transfecting Raw 264.7 macrophages
with dominant negative (DN) forms of Nod1 and Nod2, we showed that
both molecules inhibited NF-?B activation in response to HKSA. The
unexpected interference of DN Nod1 in the response of macrophages to
Gram-positive bacteria was confirmed with a Nod2 agonist (muramyl
dipeptide) in transfection experiments in HEK293T cell. Finally, HKSA
up-regulated the expression of Nod1 but not Nod2 mRNA in mouse Raw
264.7 macrophages, Our study shows the contribution of phagocytosis
for cytokine production and that of Nod2 for macrophage response to
HKSA. It also identifies a cross-talk between Nod1 and Nod2.
<snip>


OK so we've got a picture of LPS and NOD1 making flakey skin ?

OK let's see them...

41 hits: nod1 + LPS -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=lps%20nod1

9 hits using card4 + LPS
http://www.ncbi.nlm.nih.gov/pubmed?term=lps%20card4

And most of these LPS is used to induce IFN to study an effect or two.


#1 of 41

http://www.ncbi.nlm.nih.gov/pubmed/22450316
Biochem Biophys Res Commun. 2012 Mar 17.
TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the
cultured HAPI cells stimulated by LPS.

Zheng W, Zheng X, Liu S, Ouyang H, Levitt RC, Candiotti KA, Hao S.

Source
College of Animal Science and Veterinary Medicine, Jilin University,
Changchun 130062, Jilin Province, PR China; Department of
Anesthesiology, University of Miami Miller School of Medicine, Miami,
FL 33136, USA.

Abstract
A growing body of evidence recently suggests that glial cell
activation plays an important role in several neurodegenerative
diseases and neuropathic pain. Microglia in the central nervous system
express toll-like receptor 4 (TLR4) that is traditionally accepted as
the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4
signaling pathways to induce the production of proinflammatory
molecules. In the present studies, we verified the LPS signaling
pathways using cultured highly aggressively proliferating immortalized
(HAPI) microglial cells. We found that HAPI cells treated with LPS
upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-
κB (pNF-κB), TNFα and IL-1β. Silencing TLR4 with siRNA reduced the
expression of pJNK, TNFα and IL-1β, but not pNF-κB in the cells.
Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the
expression of TNFα and IL-1β. Unexpectedly, we found that inhibition
of Nod1 with ML130 significantly reduced the expression of pNF-κB.
Inhibition of NF-κB also reduced the expression of TNFα and IL-1β.
Nod1 ligand, DAP induced the upregulation of pNF-κB which was blocked
by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-
dependent, and that pNF-κB is Nod1-dependent in HAPI cells treated
with LPS. Either TLR4-JNK or Nod1-NF-κB pathways is involved in the
expression of TNFα and IL-1β.

PMID: 22450316


And i've got other FISH to fry... or try?


And we still only get one hit for erap1 and LPS.

http://www.ncbi.nlm.nih.gov/pubmed?term=lps%20erap1

http://www.ncbi.nlm.nih.gov/pubmed/21531727
J Biol Chem. 2011 Jun 17;286(24):21906-14. Epub 2011 Apr 29.
Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the
activation of macrophages induced by lipopolysaccharide and interferon-
gamma.

Goto Y, Ogawa K, Hattori A, Tsujimoto M.

Source
Laboratory of Cellular Biochemistry, RIKEN, Wako, Saitama, 351-0198,
Japan.

Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional
enzyme with an important role in processing antigenic peptides
presented to class I major histocompatibility complex in the
endoplasmic reticulum. In this study, we found that endoplasmic
reticulum-retained ERAP1 was secreted from macrophages in response to
activation by treatment with lipopolysaccharide (LPS) and interferon
(IFN)-γ and enhanced their phagocytic activity. Enhancement of the
phagocytic activity of murine macrophage RAW264.7 cells induced by LPS/
IFN-γ was inhibited by a potent aminopeptidase inhibitor, amastatin.
The addition of recombinant wild-type but not inactive mutant ERAP1 to
culture medium enhanced phagocytosis. These results suggest that
enhancement of phagocytic activity is at least in part mediated by
secreted ERAP1 through the generation of active peptides processed by
the enzyme. Our data reveal ERAP1-mediated activation of macrophages
for the first time and will provide new insights into the role of this
enzyme in innate immunity.

PMID: 21531727

Is their a chimera in the eR?

http://www.ncbi.nlm.nih.gov/pubmed/22466567
Biol Pharm Bull. 2012;35(4):601-5.
Exon 10 coding sequence is important for endoplasmic reticulum
retention of endoplasmic reticulum aminopeptidase 1.

Hattori A, Goto Y, Tsujimoto M.

Source
Laboratory of Cellular Biochemistry, RIKEN.

Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a final trimming
enzyme of N-extended antigenic peptides bound to major
histocompatibility complex class I molecules in the endoplasmic
reticulum (ER). In our previous work, we found that ERAP1 is secreted
from macrophages in response to activation by lipopolysaccharide and
interferon-γ. In this paper, we searched for the amino acid sequence
of ERAP1 protein important for ER retention by constructing chimeric
proteins and found that the sequence between 485 and 615 was
significant. Moreover, by comparing the genomic organizations of
oxytocinase subfamily members, the exon 10 coding sequence, which
might be inserted into the common ancestral gene of the oxytocinase
subfamily enzymes during evolution, was found to be important for ER
retention of ERAP1. Taken together, our data indicate that ERAP1
contains amino acid sequence important for ER retention.

PMID: 22466567
Free full text
http://joi.jlc.jst.go.jp/JST.JSTAGE/bpb/35.601?from=PubMed


randall... what just haPPened HERE? Thank-You for your Dedication
ANNE Bowcock and ALAN Menter et al.....

[JRStern]

On Fri, 20 Apr 2012 09:58:48 -0700 (PDT), randall <ranh...@aol.com>
wrote:

>Scientist (for psoriasis and genes), Anne Bowcock et al found a
>mutated CARD14 gene in PSORS2?

Googling CARD14 already turns up a ton of stuff and I don't really
know how to read any of it.

But it sounds hopeful that the information is getting more focused.

J.

http://www.genecards.org/cgi-bin/carddisp.pl?gene=CARD14

http://en.wikipedia.org/wiki/CARD14

[randall]

On Apr 20, 4:18 pm, JRStern <JRSt...@foobar.invalid> wrote:
> On Fri, 20 Apr 2012 09:58:48 -0700 (PDT), randall <ranhu...@aol.com>

> wrote:
>
> >Scientist (for psoriasis and genes), Anne Bowcock et al found a
> >mutated CARD14 gene in PSORS2?
>
> Googling CARD14 already turns up a ton of stuff and I don't really
> know how to read any of it.
>
> But it sounds hopeful that the information is getting more focused.
>
> J.
>
> http://www.genecards.org/cgi-bin/carddisp.pl?gene=CARD14
>
> http://en.wikipedia.org/wiki/CARD14

j

Thank you

I did figure out, by looking for the pmid a few minutes ago
i screwed uP big TIME..

And all morning long i figured it was excess pork making
me feel so poorly... LOL


Oh well... it's NOT NOD1 CARD4 but CARD14 aka- carma2.

And you go with what you can see or find in
old posts as to what's what i suppose.


from you genecard link:

[...] Entrez Gene summary for CARD14:
The protein encoded by this gene belongs to the membrane-associated
guanylate kinase (MAGUK) family, a class of
proteins that functions as molecular scaffolds for the assembly of
multiprotein complexes at specialized regions of
the plasma membrane. This protein is also a member of the CARD protein
family, which is defined by carrying a
characteristic caspase-associated recruitment domain (CARD). This
protein shares a similar domain structure with
CARD11 protein. The CARD domains of both proteins have been shown to
specifically interact with BCL10, a protein known
to function as a positive regulator of cell apoptosis and NF-kappaB
activation. When expressed in cells, this protein
activated NF-kappaB and induced the phosphorylation of BCL10. Two
alternatively spliced variants of this gene encoding
distinct isoforms have been reported. (provided by RefSeq)

UniProtKB/Swiss-Prot: CAR14_HUMAN, Q9BXL6
Function: Activates NF-kappa-B via BCL10 and IKK. Stimulates the
phosphorylation of BCL10
<snip>

I recognize BCL's but not the MAGUK word but Guanylate is crap iirc.
LOL

Only 291 hits for maguk in pubmed:
http://www.ncbi.nlm.nih.gov/pubmed?term=maguk

336 with the asterisk * - maguk*
http://www.ncbi.nlm.nih.gov/pubmed?term=maguk*

OK and back to BCL's triggering NK-kB via caspase?

http://en.wikipedia.org/wiki/BCL10
Symbols BCL10; CARMEN; CIPER; CLAP; c-E10; mE10
B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by
the BCL10 gene.[1][2]
This gene was identified by its translocation in a case of mucosa-
associated lymphoid tissue (MALT) lymphoma. The protein encoded by
this gene contains a caspase recruitment domain (CARD), and has been
shown to induce apoptosis and to activate NF-kappaB. This protein is
reported to interact with other CARD domain containing proteins
including CARD9, 10, 11 and 14, which are thought to function as
upstream regulators in NF-kappaB signaling. This protein is found to
form a complex with MALT1, a protein encoded by another gene known to
be translocated in MALT lymphoma. MALT1 and this protein are thought
to synergize in the activation of NF-kappaB, and the deregulation of
either of them may contribute to the same pathogenetic process that
leads to the malignancy.[2]

Interactions
BCL10 has been shown to interact with CARD10,[3] CARD11,[4] MALT1,[5]
TRAF2,[6] IKBKG[7] and CARD9.[8]
<snip>

The caspase recruitment domain (CARD) being KEY with NF-kB.

And in the MALT or galt and it's the gene's FAULT.... LoL

Finding malt..

ok

http://en.wikipedia.org/wiki/Mucosa-associated_lymphoid_tissue_(MALT)_lymphoma

i want the other malt for now..

http://en.wikipedia.org/wiki/Mucosa-associated_lymphoid_tissue
The mucosa-associated lymphoid tissue (MALT) (also called mucosa-
associated lymphatic tissue) is the diffusion system of small
concentrations of lymphoid tissue found in various sites of the body,
such as the gastrointestinal tract, thyroid, breast, lung, salivary
glands, eye, and skin.

MALT is populated by lymphocytes such as T cells and B cells, as well
as plasma cells and macrophages, each of which is well situated to
encounter antigens passing through the mucosal epithelium. In the case
of intestinal MALT, M cells are also present, which sample antigen
from the lumen and deliver it to the lymphoid tissue.

Components
The components of MALT are sometimes subdivided into the following:
GALT (gut-associated lymphoid tissue. Peyer's patches are a component
of GALT found in the lining of the small intestines.)
BALT (bronchus-associated lymphoid tissue)
NALT (nasal-associated lymphoid tissue)
CALT (conjunctival-associated lymphoid tissue)[1]

Role in disease
MALT plays a role in regulating mucosal immunity. It may be the site
of lymphoma, usually non-Hodgkin lymphoma. A specific entity is the
MALT lymphoma linked to Helicobacter pylori in the stomach.
<snip>

So malt and card14 are the target.

With that crap (maguk) stuff... which should be exposed now? i guess.

http://en.wikipedia.org/wiki/Guanylate_kinase
In enzymology, a guanylate kinase (EC 2.7.4.8) is an enzyme that
catalyzes the chemical reaction
ATP + GMP ADP + GDP

Thus, the two substrates of this enzyme are ATP and GMP, whereas its
two products are ADP and GDP.
This enzyme belongs to the family of transferases, specifically those
transferring phosphorus-containing groups (phosphotransferases) with a
phosphate group as acceptor. This enzyme participates in purine
metabolism.

Guanylate kinase catalyzes the ATP-dependent phosphorylation of GMP
into GDP.[1] It is essential for recycling GMP and indirectly, cGMP.
In prokaryotes (such as Escherichia coli), lower eukaryotes (such as
yeast) and in vertebrates, GK is a highly conserved monomeric protein
of about 200 amino acids. GK has been shown to be structurally similar
to protein A57R (or SalG2R) from various strains of Vaccinia virus

Nomenclature
The systematic name of this enzyme class is ATP:(d)GMP
phosphotransferase. Other names in common use include"
deoxyguanylate kinase,
5'-GMP kinase,
GMP kinase,
guanosine monophosphate kinase, and
ATP:GMP phosphotransferase.
<snip>


We've had a sh*t load of GMP's in the cGMP iirc.

So?

http://en.wikipedia.org/wiki/Guanosine_monophosphate
Guanosine monophosphate, also known as 5'-guanidylic acid or guanylic
acid and abbreviated GMP, is a nucleotide that is used as a monomer in
RNA. It is an ester of phosphoric acid with the nucleoside guanosine.
GMP consists of the phosphate group, the pentose sugar ribose, and the
nucleobase guanine; hence it is a ribonucleoside monophosphate.
Guanosine monophosphate is produced from dried fish or dried seaweed.

[...] As inhibitor of guanosine monophosphate synthesis in
experimental models, the glutamine analogue DON can be used.[1]
<snip>


Do we want inhibition of NF-kB or here?

On the crap deal?

It's a crap shoot... LOL

So we LOOK now at the DON of crap?

What's not to LIKE? Lol

http://en.wikipedia.org/wiki/6-Diazo-5-oxo-L-norleucine
6-Diazo-5-oxo-L-norleucine (DON) is a glutamine antagonist, which was
isolated originally from Streptomyces. It is a non-standard amino
acid. The diazo compound was characterized in 1956 by Henry W Dion et
al.,[2] who suggested a possible use in cancer therapy. This
antitumoral efficacy was confirmed in different animal models.[3] DON
was tested as chemotherapeutic agent in different clinical studies,
but was never approved. The last clinical results were published in
2008, though not as DON monotherapy but in combination with a
recombinant glutaminase
<snip>


and it looks like a clue or two in this:
http://en.wikipedia.org/wiki/6-Diazo-5-oxo-L-norleucine#Biochemistry

But my CAT is getting frisky and i can't concentrate.

To much pork since EASTER... LoL

I porked out... split pea soup right after easter and then
a pork roast and it became pork enchilada's in it's last
reincarnation.

Hey! i'm dying here...i wan't made for eating excess pork.

It must be triggering the crap CARD14, NF-kB in my BRAIN?

While my skin isn't flaky or crispy my HEAD and neuro functions
are sub par to distraction level's.

I hate that.

OK... stop RAMBLING... and find the point.

Cat is gone... that's GOOD.

Where was i?

Oh...that DON stuff.

And inhibition of NF-kB.

I suppose we simply...

go to pubmed?

oK.


LOL and one or two mentions of CARD14
in the P NG


Jays dietary thread:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/fb5864a66b44cd85?&q=card14

which is:

Wed, Dec 22 2010 5:13 pm
Subject: Re: JAYs Dietary PPAR -sniP - Kirs -FABP - Ap2 - Card11 -
Malt -Runx1 - ComPound A - Osteopontin - hike...
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/fb5864a66b44cd85


And little help.

So back to pubmed:

ONLY 14 hits for card14
http://www.ncbi.nlm.nih.gov/pubmed?term=card14

#2 of 14 has lectins dectins and NEMO...

finding nemo is always going on... LOL

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193407/figure/fig5/
from :
http://www.ncbi.nlm.nih.gov/pubmed/21187856
[...] pmid: 21187856

And i see bcl10 and malt and syk and ikk. So we're on target.

We just have to understand how a mutation in this
arena affects....

Nevermind.

Let's try NF-kB inhibition instead?

I'm like a TNF blocker now. LOL

i've gone BIG Pharma?

Yep..

time to block or run interference.

PUNT...? LOL

OK like 10,000 of these dudes

http://www.ncbi.nlm.nih.gov/pubmed?term=nf-kb%20inhibition

over 10k
http://www.ncbi.nlm.nih.gov/pubmed?term=nf-kb%20inhibitor

and by using the HERB word under 50 to 48....
http://www.ncbi.nlm.nih.gov/pubmed?term=nf-kb%20inhibitor%20herb

iirc this one looks familiar

TCM and top 50 herb's?

Chinese herb Tripterygium wilfordii Hook.f, (Triptolide)

#4 of 48 also is familiar :

http://www.ncbi.nlm.nih.gov/pubmed/21720559
Honokiol arrests cell cycle, induces apoptosis, and potentiates the
cytotoxic effect of gemcitabine in human pancreatic cancer cells.
Arora S, Bhardwaj A, Srivastava SK, Singh S, McClellan S, Wang B,
Singh AP.
PLoS One. 2011;6(6):e21573. Epub 2011 Jun 24.
PMID: 21720559



Finding hOW to sTOP NEMO is a biggy

#7 of 48

http://www.ncbi.nlm.nih.gov/pubmed/21143809
Inhibition of the NEMO/IKKβ association complex formation, a novel
mechanism associated with the NF-κB activation suppression by Withania
somnifera's key metabolite withaferin A.
Grover A, Shandilya A, Punetha A, Bisaria VS, Sundar D.
BMC Genomics. 2010 Dec 2;11 Suppl 4:S25.
PMID: 21143809


OK i'm finding LUNCH... now.


will get my CARMA2 on this thing later.... dude...


randall.. i HATE making mistakes... i need new... eye's? LOL

[JRStern]

On Sat, 21 Apr 2012 11:55:43 -0700 (PDT), randall <ranh...@aol.com>
wrote:

>And all morning long i figured it was excess pork making
>me feel so poorly... LOL

don't say 'pork', I'm trying to resist the urge to go get some spare
ribs at my local Chinese joint, omg they're good, ...

J.

[randall]

On Apr 21, 4:24 pm, JRStern <JRSt...@foobar.invalid> wrote:
> On Sat, 21 Apr 2012 11:55:43 -0700 (PDT), randall <ranhu...@aol.com>

> wrote:
>
> >And all morning long i figured it was excess pork making
> >me feel so poorly... LOL
>
> don't say 'pork', I'm trying to resist the urge to go get some spare
> ribs at my local Chinese joint, omg they're good, ...
>
> J.

jxr

It's no time for chit chat over pork FAT.

We can chew that FAT in the future.

Right NOW we've got...80% of all FLAKEs
on the table.

And it ain't DIM SUM.

http://en.wikipedia.org/wiki/Dim_sum


Not YET anyway.

So, that being said.

I'm going to go in to long deep
introspection regarding the topic(al) situation.


...

And back towards epigenetic cpg methylation

http://en.wikipedia.org/wiki/CpG_island
In genetics, CpG islands or CG islands are genomic regions that
contain a high frequency of CpG sites but to date objective
definitions for CpG islands are limited. In mammalian genomes, CpG
islands are typically 300-3,000 base pairs in length. They are in and
near approximately 40% of promoters of mammalian genes.[1] About 70%
of human promoters have a high CpG content. Given the GC frequency
however, the number of CpG dinucleotides is much lower than expected.
[2] The "p" in CpG refers to the phosphodiester bond between the
cytosine and the guanine, which indicates that the C and the G are
next to each other in sequence regardless of being single- or double-
stranded.
<snip>

http://en.wikipedia.org/wiki/Methylation
In the chemical sciences, methylation denotes the addition of a methyl
group to a substrate or the substitution of an atom or group by a
methyl group. Methylation is a form of alkylation with, to be
specific, a methyl group, rather than a larger carbon chain, replacing
a hydrogen atom. These terms are commonly used in chemistry,
biochemistry, soil science, and the biological sciences.
In biological systems, methylation is catalyzed by enzymes; such
methylation can be involved in modification of heavy metals,
regulation of gene expression, regulation of protein function, and RNA
metabolism. Methylation of heavy metals can also occur outside of
biological systems.
<snip>


Get my drift?

It's so on the TABLE now.

And time is short.

Er er er.... LOL

Is it Erap1 then?

No i'm guessing in the cytosol with
that card14/carma2 gene.


So much easier to GUESS, when theY
figure it out for us?

http://en.wikipedia.org/wiki/Cytosol


And looking at ANNE Bowcock for GRINs?


Why not?


OK is the most recent pubmed on Card14 available
beside's in CELL?

Nope.

Anne Bowcock still has 160 hits:
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bowcock%20AM%22%5BAuthor%5D

We want 161.


And if we go back it confirms my suspicion in this
thread NO LESS.


#4 of 160 is right up this alley?

Isn't it?



http://www.ncbi.nlm.nih.gov/pubmed/22071477
J Invest Dermatol. 2012 Mar;132(3 Pt 1):583-92. doi: 10.1038/jid.
2011.348. Epub 2011 Nov 10.
A subset of methylated CpG sites differentiate psoriatic from normal
skin.

Roberson ED, Liu Y, Ryan C, Joyce CE, Duan S, Cao L, Martin A, Liao W,
Menter A, Bowcock AM.

Source
Department of Genetics, Washington University School of Medicine, St
Louis, Missouri 63110, USA.

Abstract
Psoriasis is a chronic inflammatory immune-mediated disorder affecting
the skin and other organs including joints. Over 1,300 transcripts are
altered in psoriatic involved skin compared with normal skin. However,
to our knowledge, global epigenetic profiling of psoriatic skin is
previously unreported. Here, we describe a genome-wide study of
altered CpG methylation in psoriatic skin. We determined the
methylation levels at 27,578 CpG sites in skin samples from
individuals with psoriasis (12 involved, 8 uninvolved) and 10
unaffected individuals. CpG methylation of involved skin differed from
normal skin at 1,108 sites. Twelve mapped to the epidermal
differentiation complex, upstream or within genes that are highly
upregulated in psoriasis. Hierarchical clustering of 50 of the top
differentially methylated (DM) sites separated psoriatic from normal
skin samples with uninvolved skin exhibiting intermediate methylation.
CpG sites where methylation was correlated with gene expression are
reported. Sites with inverse correlations between methylation and
nearby gene expression include those of KYNU, OAS2, S100A12, and
SERPINB3, whose strong transcriptional upregulation is an important
discriminator of psoriasis. Pyrosequencing of bisulfite-treated DNA
from skin biopsies at three DM loci confirmed earlier findings and
revealed reversion of methylation levels toward the non-psoriatic
state after 1 month of anti-TNF-α therapy.

Comment in
J Invest Dermatol. 2012 Mar;132(3 Pt 1):506-8.
http://www.ncbi.nlm.nih.gov/pubmed/22327261.1

PMID: 22071477

And the comment goes to Krueger no LESS.


http://www.ncbi.nlm.nih.gov/pubmed/22327261.1
J Invest Dermatol. 2012 Mar;132(3 Pt 1):506-8. doi: 10.1038/jid.
2011.364.
A role for epigenetics in psoriasis: methylated Cytosine-Guanine sites
differentiate lesional from nonlesional skin and from normal skin.

Gudjonsson JE, Krueger G.

Source
Department of Dermatology, University of Michigan, Ann Arbor, Michigan
48109, USA. joh...@med.umich.edu

Abstract
DNA methylation is one of several epigenetic mechanisms that can lead
to stable and heritable changes in gene expression without changing
the underlying DNA sequence. In this issue, Roberson et al.
demonstrate that lesional skin in psoriasis is accompanied by changes
in DNA methylation, which revert back to baseline with treatment,
indicating that DNA methylation in psoriasis is dynamic.
Comment on
J Invest Dermatol. 2012 Mar;132(3 Pt 1):583-92.

PMID: 22327261


One of these days i'm gonna have to look
at G and JG Krueger to find out if G is father
to JG.


NPF G only has
74 hits - "Krueger G"[Author]
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krueger%20G%22%5BAuthor%5D

And JG has -159 hits
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krueger%20JG%22%5BAuthor%5D


OK, my little Girl... (cat) needs attention now... LOL

She doesn't like being in the yard with the new dog...

Darn!

And my gingko is in BLOOM and i can smell a faint...delicious
odor.

And the parrots are going to town on the loquats.

http://en.wikipedia.org/wiki/Ginko_biloba
http://en.wikipedia.org/wiki/Loquat

My little sweet heart can't get to those pesky
Parrots and that is a dilemma, i'm guessing.

Maybe i should shot one and see what she does with it?

Her brother will beat her to it for sure.

And both will LOSE interest i'm guessing.

So... NO WAY am i gonna pop a parrot?

http://en.wikipedia.org/wiki/Parrot

These don't look like mine.

Their

more like
http://www.photosshow.com/eclectus-parrot-2/

OK just like these:
http://www.sandiegotraveltips.com/public/Wild_Parrots_of_San_Diego.cfm

http://www.sandiegotraveltips.com/public/images/477a.jpg


Noisy little DEALs...

Give me a gray from the Congo over these dudes any day.

http://en.wikipedia.org/wiki/African_Grey_Parrot


I met one in the store and asked his owner if he spoke.

And the bird said... he can't fly and rarely speaks...


I thought... nice bird...


Want to go home with me and meet my critters?




randall... life isn't EASY... and or xyz... but Bowcock is on
track..nice!

[JRStern]

On Sat, 21 Apr 2012 18:50:28 -0700 (PDT), randall <ranh...@aol.com>
wrote:

>I'm going to go in to long deep
>introspection regarding the topic(al) situation.

Speaking of topicals, I've been meaning to post something about Dove
bodywash "with Nutrium moisture", whatever that means.

Whatever it is (and I don't think it's any new chemical, just a
marketing term), I started using this stuff recently and it seems a
much better approach than the harsher soaps I was using before, seems
to markedly reduce flaking.

I wash with this stuff, used liberally, and then after drying I
slather on the Curel, and between the two the psoriasis is much better
managed than without either.

The Dove bodywash comes in about a dozen flavors, including some in
grey bottles "for men", with only the most minor variations in
ingredients, but I just noticed one I picked up with "cucumber and
green tea scent" also contains hydrogenated soybean oil (not in the
base versions of the product), not sure I like that rubbing trans-fats
all over my skin. Gotta read the small print before buying these
things.

J.

[Bohgosity BumaskiL]

Hydrogenated soybean oil iz not necessarily trans fat. Trans fat is
a lower-energy change on a double bond from cis fat. It occurs upon
merely heating an unsaturated oil, which iz why I do not trust the
trans fat free claims on potato chips. That and the fact that
Google(nutrition data) haz no numbers on trans fat in potato chips
fried in soybean oil.
_______
Think of a vulture. Why do you think it looks that way? It doesn't
eat water rich foods. If you eat something that's dried and dead,
then what are you going to look like? I'm only half kidding on this
point.
--Anthony Robbins