Glycosylation is defined as "the enzyme-catalyzed covalent attachment of a carbohydrate to a polypeptide, lipid, polynucleotide, carbohydrate, or other organic compound, generally catalyzed by glycosyltransferases, utilizing specific sugar nucleotide donor substrates."
This article talks about how glycosylation relates to cancer. Specific glycan structures are common markers for tumor progression, and altered glycosylation is "a universal feature of cancer cells."
There are many forms of glycan changes in malignant cells. Examples include loss of expression, excessive expression of certain structures, persistence of incomplete structures, accumulation of precursors, and the appearance of novel structures. Of all possible glycan biosynthetic changes, only a few are commonly correlated with malignant transformation and tumor progression. Because cancer is a microevolutionary process, that only allows the fittest cells in a population to survive, the article proposes that "these specific glycan changes are selected for during tumor progression." The author later describes the most frequent changes, considering the likely biosynthetic mechanisms and the feasible biological consequences.
Proteins are generally encoded by a single gene. Unlike proteins, a glycan determinant is made by the collaborative action of several related genes. This makes it difficult to explain in detail the genetic regulatory mechanism for expression of some cell-surface glycans. There has been an increase of knowledge on the transcriptional background of cancer-associated glycan alteration from the availability of the human genome sequence, application of DNA microarray, and other molecular biological techniques to glycosyltransferases and related genes.
Various examples have demonstrated a direct association between glycan alteration and the genetic mechanism for malignant transformation of cells. One example is transcriptional induction of MGAT5 (the gene for GlcNAc transferase-V) by v-src, H-ras, and v-fps. An additional example is enhanced expression of sialyl Lewis on adult T-cell leukemia cells. They're known to have very strong tissue infiltrative activity, likely settled by selectins. The transcription activator protein, Tax, binds to the 5' regulatory region of the gene for fucosyltranserease-7, and activates its transcription. This also exemplifies the direct associated between glycan alteration and malignant transformation.
"Hold Your Wee for a Wii"
Water composes approximately 2/3 of the human body; running through blood, inhabiting cells, and enclosing the spaces between. The body constantly loses water through sweat, urination, defecation, and exhaled breath, to name a few routes. It's imperative to replace this loss but it is possible to overdo rehydration, and even have a fatal water overdose.
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| Jennifer Strange |
In 2007, Jennifer Strange, a 28 year old woman from California died after participating in a radio contest. The contest, titled "Hold Your Wee for a Wii," forced contestants to drink increasing amounts of water every 10-15 minutes. Strange drank six liters of water in three hours, vomited, and went home complaining of a headache. It was so excruciating that she called a co-worker, crying in pain. A few hours later she was found dead of water intoxication.
Hyponatremia is defined as an insufficient amount of salt in the blood. The normal blood sodium concentration is between 135 and 145 millimoles per liter. Hyponatremia is when a blood sodium falls below 135 millimoles per liter. Severe occurrences of hyponatremia can lead to water intoxication.
The kidneys control the amount of water, salts, and other solutes that leave the human body. When someone drinks excessive water in a short amount of time, the kidneys cannot drain it quickly enough and the blood becomes saturated with water. The overabundance of water leaves the blood and eventually enters the cells, which expand to provide space for it. However, neurons do not have the room to stretch. Brain cells are packed tightly inside the skull, and there is very little space for cells to expand and swell. Brain edema, which is swelling of the brain, can be catastrophic. Rapid and severe hyponatremia can lead to seizures, brain stem herniation, and death.
If you would like to read more about Jennifer Strange's story, check out this article. If you would like to learn more about water intoxication, go to this Scientific American article.
2011 Nobel Prize Winners
The 2011 Nobel Prize winners were announced last Monday, October 3rd. This year's Nobel Prize in Physiology or Medicine was awarded to Bruce Beutler, Jules Hoffman and Ralph Steinman. Beutler and Hoffman helped to clarify innate immunity, "the non-specific array of initial responses by the body's immune system that can recognize invading microorganisms as being foreign and try to destroy them." Steinman researched dendritic cells and their importance in adaptive immunity, "the specialized response to specific invaders" that become involved when innate immunity needs assistance.
The detailed intellect of the immune system will help researchers improve vaccines and provide new attempts to excite immune reactions to cancer.
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| Ralph Steinman |
This raised questions about Steinman's award, because the Nobel Committee rules state "the prize can be awarded posthumously only if the laureate dies between the October announcement and the award ceremony, held annually on December 10 in Stockholm, Sweden." The committee was apparently unaware of Steinman's death, and The Rockefeller University only learned of the news on Monday. However, the Nobel foundation announced that Steinman would remain a prize winner.
After all, I think it would be way too harsh for his family if the Nobel foundation were to revoke his prize. The man clearly deserved it, and the date of his death (which was only 3 days before the announcement) shouldn't affect his accolade. To read about the Nobel Prize winners, click on this article. To go to the Nobel Prize website, click here.
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