Journal Club: Dentistry, Biochemistry, Cancer Biology, and Neuroscience

Thursday, October 4, 2012

DENTISTRY: Effects of xylitol wipes on cariogenic bacteria and caries in young children. Zhan, L. et al. (Featherstone). Journal of Dental Research 91:85S-90S.

Xylitol is a natural sugar substitute that has about the same sweetness as sucrose and is often added to sugar free gum, toothpaste and some pharmaceuticals as a sweetener. Multiple studies have suggested that xylitol may inhibit the harmful bacterial growth that causes dental caries (cavities) and may also promote remineralization of teeth before cavities form. Tooth brushing and flossing remain more effective ways to combat cavity formation, but adding xylitol to things like chewing gum appears to help prevent dental caries.

The American Academy of Pediatric Dentistry recommends that infants and toddlers use dental wipes as opposed to tooth brushing (as infants do not yet have teeth) and the researchers here wanted to determine whether adding xylitol to these wipes could help prevent cavity formation by inhibiting bacterial growth. Interestingly, they found that while infants and toddlers who used xylitol wipes had significantly fewer dental caries compared to those using wipes without xylitol, there was no difference in the bacterial content of the mouth – indicating that xylitol was effective, but not due to an inhibition of bacterial growth.

BIOCHEMISTRY: Engineering a model protein cavity to catalyze the Kemp elimination. Merski, M., Shoichet, B.K. Proceeds of the National Academy of Science, Sept. 17. [Epub ahead of print]

Engineering proteins from scratch to catalyze specific chemical reactions is hard work. How do you design a protein from a set of 20 amino acids, each with unique chemical properties, into a third <or 3D? not sure> structure that can interact with – and alter – another molecule? Enzyme engineering has huge potential in a wide range of chemistry applications. Most studies that attempt to generate novel enzymatic properties of a molecule utilize intense computational chemistry or are limited by attempting to mimic enzymes already found in nature, and often result in equally complicated enzyme products where it is difficult to identify where and how structure influences function. To generate a simplified, novel enzyme to catalyze the “Kemp elimination,” researchers first identified what simple type of environment was most helpful for the Kemp reaction to occur: polar and aprotic. Then they identified an existing enzyme with a polar and aprotic active site: a slightly mutated T4 lysozyme. Using their extensive experience in biochemistry, the researchers made slight mutations to the lysozyme that enhanced both its stability and its ability to catalyze the Kemp elimination, resulting in a simplified protein structure that has significant enzymatic activity.

CANCER BIOLOGY: Characterization of a diffuse intrinsic pontine glioma cell line: implications for future investigations and treatment. Hashizume, R. et al. (Gupta). Journal of Neurooncology, Sept. 17. [Epub ahead of print]

Diffuse intrinsic pontine gliomas are a class of brain tumor that grow within networks of neurons (“diffuse,” as opposed to a solid tumor) of the pons in the brainstem (hence “pontine”) and contain glial cells, which support and protect neurons in the brain. This type of glioma typically arises in children and has a poor prognosis because of the location of the tumor (it cannot be surgically removed) and its ultimate resistance to treatment with chemotherapy and radiation. Very little is known about the genetic mutations underlying this type of glioma because few biopsy and autopsy specimens are available. Knowing the genetic mutations found in these gliomas may lead to new treatments, some of which may already be in use for other forms of cancer. Therefore, there is much interest in developing a model of this cancer that can be examined in the lab. Here, researchers describe a cell line generated from a patient’s diffuse intrinsic pontine glioma that is capable of creating similar tumors in mice without immune systems (because the human cells would otherwise be rejected). This represents the first model of this type of glioma that can now be studied extensively in the lab.

NEUROSCIENCE: Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes. Reyes, R.C.; Brennan, A.M.; Shen, Y.; Baldwin, Y.; Swanson, R.A. Journal of Neuroscience, 32(37):12973-8.

Too much excitation of neurons can be lethal – excessive signaling in a neuron via neurotransmitters initiates signaling cascades that allow harmful levels of calcium to enter the cell and causes the production of harmful superoxides, both of which contribute to initiate apoptosis. One oversimplified example of this “excitotoxicity” is hearing loss following exposure to loud music – the loud music causes huge levels of neurotransmitters to be released to auditory nerve cells, resulting in some cell death and some hearing loss. One question remaining has been whether all of the dying cells directly received a toxic dose of neurotransmitters, or whether some of the cells die due to the release of harmful superoxides from nearby dying cells. To test this, researchers made a mixture of cells that could generate superoxides in response to overstimulation with cells that could not and looked at which cells died in response to overstimulation. They found that all of the responder cells died with overstimulation, and non-responder cells sitting next to responder cells also died. These results indicate that excitotoxicity includes cell death directly caused by overexcitation from neurotransmitters and cell death caused by the release of superoxides by nearby dying cells.