Temperature extremes affect PGI and physiological performance

Santa Clara University biology professor Elizabeth Dahlhoff lectured at Dartmouth as a part of the biology department’s Fall 2010 Cramer Seminar Series. Her research focuses on temperature adaptation and climate variation, and she has recently studied the herbivorous Willow Leaf Beetle in the High Sierra region of California.  Because the beetles are ectotherms, their internal body temperature, genetic diversity, and performance are all linked to the thermodynamics of nature.

Dahlhoff looked at the “1” and “4” alleles of the polymorphic gene for the enzyme, PhosophoglucoseIsomerase (PGI), which converts glucose-6-phosphate to fructose-6-phosphate in glycolysis. The beetles’ performance in extreme climates is related to how well they cope, and the different forms of PGI are related to expression of heat shock proteins, which recover and refold proteins that unfold in extreme temperatures.

The “1” allele is cold adapted and the “4″ allele is warm adapted.

Dahlhoff also studied how the gene itself changes physiological performance. When exposed to either -4°C (cold extreme), 20°C (normal), or 36°C (hot extreme), the 1-1 beetles were able to run faster than the 4-4 beetles, but upon a second extreme exposure (-4 or 36), the 4-4 beetles were able to up-regulate heat shock proteins and increase running speed. In addition, 1-1 beetles laid more eggs in colder areas, while 4-4 beetles laid more eggs in warmer sites.

Dahlhoff claimed, “The ultimate fate of organisms relies on their ability to adapt to extremes throughout the year.”


Radiologists increasingly use computer-aided detection for mammography interpretation

A team of Dartmouth Medical School researchers, led by Tracy Onega, recently conducted a study on radiologists’ perception of computer-aided detection versus double reading for mammography interpretation.  Their findings were published in Academic Radiology.

Mammography Image

Mammography Image

The traditional method of double reading by a second clinician in screening mammography interpretation may soon be replaced by computer-aided detection (CAD) of breast cancer.

Despite the diffusion of CAD in clinical practice, there is limited and contradictory information as to its relative harms and benefits. Thus, the different perceptions of CAD and double reading are likely to have implications for the variability and performance in mammography interpretation. The researchers mailed a survey to 257 community radiologists to assess their perceptions and practices regarding CAD and double reading. The data was analyzed by classifying the radiologists’ perception of both practices based on their relative agreement or disagreement with several statements specific to CAD and double reading.

The results showed that 64% of radiologists used CAD for more than half the screening mammograms they interpreted while only fewer than 5% said the same for double reading. However, more radiologists believed that double reading improved cancer detection rates as compared to CAD. At the same time, more radiologists were likely to think that CAD decreased recall rates rather than double reading. Perhaps not surprisingly, it was also found that those radiologists with the most favorable perceptions of CAD had significantly higher uses of CAD, greater workload in screening mammography, academic affiliation, and fellowship training.


When vision is on the line: initial treatment of pigmentary glaucoma

David Campbell, an ophthalmologist at Dartmouth-Hitchcock Medical Center, published addresses the challenges of treating the second most common cause of blindness worldwide in his publication, “Initial Treatment of Pigmentary Glaucoma.” Glaucoma, a condition involving damage to the ocular nerve, is typically the result of fluid pressure build-up in the eye resulting from blockage of aqueous humour flow between the cornea, the iris and the lens. The progression and causes of glaucoma vary between patients, as glaucoma encompasses many diseases.

Campbell describes treatment options for a hypothetical patient experiencing glaucoma as a result of pigmentary dispersion syndrome, in which fluid circulation is inhibited by eye pigment flaking off the iris.  According to Campbell, reducing intraocular pressure must be a priority in treating the glaucoma, to reduce the possibility of further damage to the patient’s field of vision. To bring about such a reduction, Campbell recommends initially prescribing a β-blocker, a class of drugs that reduces intraocular pressure by lowering production of aqueous humor. Should symptoms persist after the β-blocker treatment regimen, the patient would be placed on a miotic, which contracts the pupil, restores the flow of aqueous humor and prevents further flaking of pigment by flattening the iris. Finally, Campbell suggests surgery such as laser iridectomy as an alternative to medication.

Brain Sciences

Consequences of Gestational Stress on Respiratory Control Development


Serontonin neurons are important in modulating respiratory activity. Image courtesy of CreativeCommons Attribution-ShareAlike

Laval University professor of Pediatrics Richard Kinkead recently spoke at Dartmouth on his research in gestational stress (GS).  Kinkead claimed that while the neuroendocrine response of releasing cortisol under stress prepares us for “fight-or-flight,” too great of cortisol levels could be harmful.  In the case of a pregnant mother, high cortisol levels is linked with preterm birth, which leads to many cases of birth defects.  These include respitartory instability, apnea, and bradycardia, a slow-beating heart.

The fetus is very sensitive to its environment during its rapid growth, and because its environment is filled with hormones and other chemicals, it is prone to morbidity from maternal GS.  Kinkead studied rat models, and induced stress periodically by exposing pregnant mothers to the odor of a predator.  Pups were tested after they were born; Kinkead found that GS lowers birth weight and reduces the response to not having enough oxygen.  This implies GS may cause sudden infant death syndrome (SIDS).

These results prompted further experimentation into 5-HT neurons (brain cells), which are important in modulating respiratory activity and are highly sensitive to stress. The results showed that GS significantly affects the development of these 5-HT neurons, perhaps from a reduction in serotonin.  Kinkead plans to study the effects of GS into adulthood.


Wu develops streamlined synthesis of allylic thioesters

Chemistry graduate student Forest Robertson and professor Jimmy Wu recently published a paper in Organic Letters. The paper focused on the synthesis of allylic thioethers from phosphorothioate ethers and alcohols. Thioethers are important biological and pharmaceutical agents, and Wu and Robertson were able to create thioethers in a single step by adding an exogenous alkoxide. No malodorous sulfur-containing compounds were required in the thioether synthesis.

Proposed Mechanism

Image courtesy of Jimmy Wu

Wu and Robertson assert the reaction proceeds via an S­N2 mechanism, which begins with the alkoxide attacking the phosphorothioate ether to create both a phosphate and a thiolate.Thiolate then displaces the phosphate to yield the intended thioether.  Wu and Robertson supported the SN2 conclusion with a nearly perfect yield of a stereoselective reaction. This improved method allows for a way to use readily available material to form molecules essential to the activity of many cancer-fighting drugs