Engineering
Nanoparticle-induced hyperthermia studied as cancer treatment option
Magnetic nanoparticles may represent a viable cancer treatment alternative, Dartmouth Medical School and Thayer School of Engineering professor Jack Hoopes reported with colleagues external to Dartmouth in the Journal of Physics D: Applied Physics. The nanoparticles can be implanted in a tumor site and exposed to an alternating magnetic field. The resulting physical interaction produces heat, which can kill the proximal tumor cells. According to the study’s introduction, a 6ºC change in temperature is capable of terminating cancer cells.
Induced hyperthermia has long been explored in cancer research, although this study appears to be one of the first applications of nanoparticle technology to effect this treatment.
The researchers focused on what settings should be employed for effective treatment and how the magnetic field interaction with the iron nanoparticles affects tissue physiologically. The amount of heat generated and the extent of the induced hyperthermia is determined by the strength of the alternating magnetic field and the specific absorption rate of the nanoparticles, which refers to the rate at which energy is absorbed. The heat must be great enough to kill the cancer cells, but not so high as to damage the surrounding tissue.
The study found that the nanoparticles appeared to have a “global” effect in treated mice; the heat generation was not localized only to cancerous tissue. Still, the treatment also appeared to avoid some of the negative physiological effects that are evident with traditional, non-nano hyperthermic treatment. (1)
Bacteria engineered to produce ethanol
A team of researchers at the Thayer School of Engineering and the Biology Department has genetically altered the bacteria Thermoanaerobacterium saccarolyticum to produce ethanol at a high yield, which has wide-ranging implications for the ongoing search for practical alternative fuel sources. The researchers reported in the Proceedings of the National Academy of Science that by knocking out the thermophilic anaerobic bacteria’s genes involved in organic acid synthesis, the bacteria would only produce ethanol.
Moreover, the researchers found that the bacteria strain was stable for at least 150 generations, making it a viable option for future biofuel endeavors.
“Our results extend the frontier of metabolic engineering in thermophilic hosts, have the potential to significantly lower the costs of cellulosic ethanol production, and support the feasibility of further cost reductions through engineering a diversity of host organisms,” the authors wrote.
The team is led by Dartmouth professor Lee Lynd, founder of the biofuel company Mascoma Corporation, which is based in Lebanon, N.H. (2)
Medicine
Link between gene expression and scleroderma found (WebExtra)
The various forms of the autoimmune disease scleroderma can be characterized by differences in gene expression in addition to clinical observations, a team of Dartmouth researchers led by genetics professor Michael Whitfield reported in July in the journal PLoS One.
Scleroderma is a chronic disease that results in abnormal deposits of collagen in the body’s connective tissues. While often disabling, it can also be fatal.
Whitfield and his colleagues compared gene expression in 34 individuals using biopsies from the forearm and back. They found that the traditional system of classifying scleroderma almost wholly on physical exam findings is non-specific as there appear to be at least three genetic subtypes within the most serious form of the disease, systemic sclerosis with diffuse scleroderma.
These findings should pave the way for more targeted treatment programs. The differences in gene expression can also be used to predict the prognosis of specific cases with greater accuracy. (3)
DMS profs: drug-coated stents safe (WebExtra)
Amid growing concern that drug-coated stents — mesh tubes surgically implanted to keep arteries open — carry an increased risk of blood clots in comparison to stents without a coating, Dartmouth Medical professors David Malenka and Aaron Kaplan found they lead to no increased risk of mortality.
The professors’ clinical study, reported in the Journal of the American Medical Association, relied on an analysis of over 60,000 Medicare patients and focused on differences in rates of survival, heart attack, and repeat procedures. They concluded that the drug-coated stents lead to fewer surgeries to reopen arteries. No difference was evident between the two forms of the device in terms of patient survival. (4)
Psychology
Smoking imagery in movies is associated with smoking behavior in middle-income countries
While several studies have concluded in recent years that there is a clear correlation between the prevalence of smoking in movies and smoking behavior in society, little is known about whether this trend holds true in middle-income countries.
Dartmouth Medical School professor James Sargent, along with colleagues in Mexico and from the University of South Carolina, conducted a survey of 3,876 Mexican secondary school students on smoking behavior and their exposure to 42 specific films.
The study, as reported in the American Journal of Preventative Medicine, found that the students were exposed to an average of 51 minutes of smoking in the films they watched. About 12 percent were current smokers and 59 percent reported that they had never smoked. The quartile of students with the highest level of exposure to smoking in movies had significantly increased odds for having ever smoked. (5)
Situational evaluations limit the negative effects of working alone
Individuals gain solo status when they are alone in a social category within a group, Tuck School of Business professor Judith White explains in the introduction to her study, published in Personality and Social Psychology Bulletin. Solo status can increase stress, which often affects performance negatively.
Solos can mitigate the effects of stress by “coping,” which can be observed in the form of cognitive appraisals. These appraisals are “evaluation[s] of the potential significance of a situation, along with one’s ability to control it,” White writes.
White found that solos who make positive evaluations, or challenge appraisals, maintain high levels of performance, which is not the case with those who make negative evaluations, also known as threat appraisals. White noted, however, that her survey sample may be skewed as those who choose to be solos could be innately more likely to make challenge appraisals. (6)
Biology
Graft tolerance in mice is mediated by T-cell subset (WebExtra)
The enzyme Granzyme B (GZB) is necessary for the development of skin graft tolerance in mice, Dartmouth Medical School researchers reported in the Journal of Immunology.
The researchers, led by microbiology and immunology professor Randy Noelle, found that tolerance could not be established in GZB knockout mice or in mice that over-express the GZB inhibitor, serine protease inhibitor 6. This proved true even when the mice were treated with anti-CD154 and other compounds that have been shown to induce tolerance.
The findings also shed light on the mechanism involved in this phenomenon. In short, GZB+ T-regulatory cells, which are traditionally involved in the process of immunosuppression, were found to infiltrate tolerant skin grafts. The researchers discovered that GZB expression by these cells specifically was instrumental in leading to tolerance by creating a chimeric mouse that was deficient in T-reg GZB expression, with normal GZB expression elsewhere. Graft survival was greatly reduced in these cases. (7)
Circadian rhythm develops earlier than thought in plants (WebExtra)
Traditionally, scientists have been able to understand little of how and when circadian rhythms develop in plants, including what conditions are necessary for this phenomenon to occur. Past attempts at solving this mystery have centered on analysis of mRNA levels as an indication of “clock” gene expression. This kind of assay, as professor C. Robertson McClung and colleagues report in Plant Physiology, may be inaccurate as it does not take into account post-transcriptional regulation of the RNA, which would reduce its abundance.
Pinpointing the initiation of clock genes could have wide-ranging effects for plant research, as scientists have long assumed that experiments can start after seedlings are allowed to grow for two days without any expression and direction from the clock genes. As McClung said in an interview with the DUJS, “if a clock is gating the responsiveness to a stimulus, then the time the stimulus is administered matters.”
By using the luciferase protein to track mRNA expression, McClung was able to conclude that clock genes are active as early as two days after seeds are first hydrated. Luciferase, endogenous to fireflies, provides for the generation of green fluorescence in vivo. (8)
References
1. C. L. Dennis et al., J. Phys. D: Appl. Phys. 41, 134020 (2008).
2. A. J. Shaw et al., PNAS. 105, 13769-13774 (2008).
3. A. Milano, et al., PLoS One. 3, e2696 (2008).
4. D. J. Malenka, A. V. Kaplan, F. L. Lucas, S. M Sharp, J. S. Skinner, JAMA 299, 24 (2008).
5. J. F. Thrasher, C. Jackson, E. Arillo-Santillan, J. Sargent, Am. J. of Prev. Med. 35, 95-102 (2008).
6. J. B. White, Personality and Social Psychology Bulletin 34, 1171-1184 (2008).
7. D. C. Gondek et al., Transplantation Survival Is Maintained by Granzyme B+ Regulatory Cells and Adaptive Regulatory T Cells. J. Immuno. 181, 4752-4760 (2008).
8. P. A. Salome, Q. Xie, C. R. McClung, Plant Phys. 147, 1110-1125 (2008)
Thumbnail images: Cigarette from http://commons.wikimedia.org/wiki/Image:Lit_cigarette.jpg. Firefly courtesy Terry Priest. Cellulose from http://en.wikipedia.org/wiki/Image:Cellulose-3D-balls.png
Correction (Dec. 3, 2008): The original article incorrectly stated that prof. Jack Hoopes was affiliated with the Tuck School of Engineering. He is actually affiliated with Dartmouth Medical School and the Thayer School of Engineering. Similarly, the team that engineered bacteria to produce ethanol is affiliated with Thayer School of Engineering, not the Tuck School of Engineering.