Song that made me cry!

I’m jealous of the rain
That falls upon your skin
It’s closer than my hands have been
I’m jealous of the rain
I’m jealous of the wind


That ripples through your clothes
It’s closer than your shadow
Oh, I’m jealous of the wind
‘Cause I wished you the best of
All this world could give
And I told you when you left me
There’s nothing to forgive
But I always thought you’d come back, tell me all you found was
Heartbreak and misery
It’s hard for me to say, I’m jealous of the way
You’re happy without me
I’m jealous of the nights
That I don’t spend with you
I’m wondering who you lay next to
Oh, I’m jealous of the nights
I’m jealous of the love
Love that was in here
Gone for someone else to share
Oh, I’m jealous of the love
‘Cause I wished you the best of
All this…
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https://goo.gl/qnp2yN

Cancer Genetics(part 1)

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PALLADIN AND THE SPREAD OF CANCER

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Pancreatic cancer is among the most serious of all cancers.
Although only the eleventh most common form
of cancer, with about 43,000 new cases each year in the
United States, pancreatic cancer is the fourth leading cause
of death due to cancer, killing more than 36,000 people
each year. Most people with pancreatic cancer survive
less than 6 months after the cancer is diagnosed; only 5%
survive more than 5 years. A primary reason for pancreatic
cancer’s lethality is its propensity to spread rapidly to
the lymph nodes and other organs. Most symptoms don’t
appear until the disease is advanced and the cancer has
invaded other organs. So what makes pancreatic cancer so
likely to spread?


In 2006, researchers identified a key gene that contributes
to the development of pancreatic cancer—an important
source of insight into pancreatic cancer’s aggressive nature. Geneticists at the University
of Washington in Seattle had found a unique family in which nine members over three
generations were diagnosed with pancreatic cancer (Figure 23.1). Nine additional family
members had precancerous growths that were likely to develop into pancreatic cancer. In
this family, pancreatic cancer was inherited as an autosomal dominant trait.
Using gene-mapping techniques, the geneticists determined that the gene causing
pancreatic cancer in the family was located within a region on the long arm of chromosome
4. Unfortunately, this region encompasses 16 million base pairs and includes
250 genes.
To determine which of the 250 genes in the delineated region might be responsible for
cancer in the family, researchers designed a unique microarray (see Chapter 20) that contained
sequences from the region. They used this microarray to examine gene expression
in pancreatic tumors and precancerous growths in family members, as well as in sporadic
pancreatic tumors in other people and in normal pancreatic tissue from unaffected people.
The researchers reasoned that the cancer gene might be overexpressed or underexpressed
in the tumors relative to normal tissue. Data from the microarray revealed that the most
overexpressed gene in the pancreatic tumors and precancerous growths was a gene encoding
a critical component of the cytoskeleton—a gene called palladin. Sequencing demonstrated
that all members of the family with pancreatic cancer had an identical mutation in
exon 2 of the palladin gene.
The palladin gene is named for
Renaissance architect Andrea Palladio
because palladin plays a central role in the
architecture of the cell. Palladin protein
functions as a scaffold for the binding of the
other cytoskeleton proteins that are necessary
for maintaining cell shape, movement,
and differentiation. The ability of a cancer
cell to spread is directly related to its cytoskeleton;
cells that spread typically have
poor cytoskeleton architecture, enabling
them to detach easily from a primary tumor
mass and migrate through other tissues. To
determine whether mutations in the palladin
gene affect cell mobility, researchers genetically engineered cells with a mutant copy of the
palladin gene and tested the ability of these cells to migrate. The cells with mutated palladin
were 33% more efficient at migrating than cells with normal palladin, demonstrating that the
palladin gene contributes to the ability of pancreatic cancer cells to spread.
The discovery of palladin’s link to pancreatic cancer
illustrates the power of modern molecular genetics for
unraveling the biological nature of cancer. In this chapter,
we examine the genetic nature of cancer, a peculiar disease
that is fundamentally genetic but is often not inherited. We
begin by considering the nature of cancer and how multiple
genetic alterations are required to transform a normal cell
into a cancerous one. We then consider some of the types
of genes that contribute to cancer, including oncogenes
and tumor-suppressor genes, genes that control the cell
cycle, genes in signal-transduction pathways, genes encoding
DNA-repair systems and telomerase, and genes that, like
palladin, contribute to the spread of cancer. Next, we take a
look at chromosome mutations associated with cancer and
genomic instability. We examine the role that viruses play in
some cancers and epigenetic changes associated with cancer.
Finally, we take a detailed look at how specific genes contribute
to the progression of colon cancer.

Catalytic Antibodies

Catalytic antibodies are antibodies that can enhance a couple of chemical and metabolic reactions in the body by binding a chemical group, resembling the transition state of a given reaction. Catalytic antibodies are produced when an antibody is immunized with a hapten molecule. The hapten molecule is usually designed to resemble the transition state of metabolic reaction. Antibodies act like soldiers to the body, fighting unwanted materials. They are secreted, for instance, when the body is infected with a bacterium or virus.


The animal produces antibodies with binding sites that are exactly complementary to some molecular feature of the invader. The antibodies can thus recognize and bind only to the invader, identifying it as foreign and leading to its destruction by the rest of the immune system. Antibodies are alsoelicited in large quantity when an animal is injected with molecules, a process known as immunization. A small molecule used for immunization is called a hapten. Ordinarily, only large molecules effectively elicit antibodies via immunization, so small-moleculehaptens must be attached to a large protein molecule, called a carrier protein, prior to the actual immunization. Antibodies that are produced after immunization with the hapten-carrier protein conjugate are complementary to, and thus specifically bind, the hapten.Ordinarily, antibody molecules simply bind; they do not catalyze reactions. However, catalytic antibodies are produced when animals are immunized with hapten molecules that are specially designed to elicit antibodies that have binding pockets capable of catalyzing chemical reactions. For example, in the simplest cases, binding forces within the antibody binding pocket are enlisted to stabilize transition states and intermediates, thereby lowering a reaction’s energy barrier and increasing its rate.This can occur when the antibodies have a binding site that is complementary to a transition state or intermediate structure in terms of both three-dimensional geometry and charge distribution. This complementarity leadsto catalysis by encouraging the substrate to adopt a transition-state-like geometry and charge distribution. Not only is the energy barrier lowered for the desired reaction, but other geometries and charge distributions that would lead to unwanted products can be prevented, increasing reaction selectivity.Making antibodies with binding pockets complementary to transition states is complicated by the fact that true transition states and most reaction intermediates are unstable. Thus, true transition states or intermediates cannot be isolated or used as haptens for immunization. Instead, so-called transition-state analog molecules are used. Transition-state analog molecules are stable molecules that simply resemble a transition state (or intermediate) for a reaction of interestin terms of geometry and charge distribution. To the extent that the transition-state analog molecule resembles a true reaction transition state or intermediate, the elicited antibodies will also be complementary to that transition state or intermediate and thus lead to the catalytic acceleration of that reaction.
Catalytic antibodies bind very tightly to the transition-state analog haptens that were used to produce them during the immunization process.
The transition-state analog haptens only bind and do not react with catalytic antibodies. It is the substrates, for example, theanalogous ester molecules, that react. For this reason, transition-state analog haptens can interfere with the catalytic reaction by binding in the antibody binding pocket, thereby preventing any substrate molecules from binding and reacting. This inhibition by the transition-state analog hapten is always observed with catalytic antibodies, and is used as a first level of proof that catalytic antibodies are responsible for any observed catalytic reaction.The important feature of catalysis by antibodiesis that,
unlike enzymes, desired reaction selectivity can be programmed into the antibody by using an appropriately designed hapten.
Catalytic antibodies almost always demonstrate a high degree of substrate selectivity.
In addition, catalytic antibodies havebeen produced that have regioselectivity sufficient to produce a single product for a reaction in which other products are normally observed in the absence of the antibody.Finally, catalytic antibodies have been producedby immunization with a single-handed version (only left- or only right-handed) of a hapten, and only substrates with the same handedness can act as substrates for the resulting catalytic antibodies. The net result is that a high degree of stereoselectivity is observed in the antibody-catalyzed reaction.Abyzymes are artificial catalytic antibodies and come from the words “antibody” and “enzyme” They are monoclonal antibodies that have catalytic properties, or carry out catalysis. The figure bellow shows the active of site of the abyzyme chorismate mutase and side-chain interactions with the transition state analog.Last modified on 14 December 2010, at 22:21Wikibooks ™MobileDesktopContent is available underCC BY-SA 3.0u