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September 17, 2015

Research Notes

Novel way to ID pathogens

There are plenty of ways in the lab to determine which bug is bugging you when you’re sick. Chemistry faculty members Xinyu Liu and Sanford Asher in the Dietrich School of Arts and Sciences, and their colleagues may have found a faster method.

Says Liu: “You can do a swab and culture the bacterium or fungi, but that takes days. You can examine the DNA, but that takes another day or two. It’s a pretty tedious process. So, before the identity of the pathogen can be determined, doctors give infected people a broad-spectrum antibiotic that kills everything.”
It would be better for the patient if physicians could correctly identify the pathogen in question as soon as possible and treat it with a specific antibiotic aimed directly at the offending bug.

Liu, Asher and colleagues have developed a method of identifying pathogens that relies on spectroscopy: determining an object’s identity through the type of light it emits. Their work was published in Angewandte Chemie International Edition.

Their team developed a specifically engineered protein hydrogel that interacts with carbohydrates on the surface of a fungus named Candida albicans, which is responsible for oral thrush and skin yeast infection and can be life-threatening for immunocompromised patients.

When the protein hydrogel interacts with the carbohydrates on the surface of C. albicans, it shrinks the 2-D photonic crystals where the hydrogel resides, emitting a specific light signature that can be recognized by the naked eye. This happens almost immediately, much faster than the days other methods require.

The broader implications are large, the researchers maintain. If they try to extend this work, they may be able to use differing antibodies to make hydrogels tailored for specific pathogens such as staph and E. coli. People living in rural areas or underdeveloped countries might be able to use this method to see if their food or water is contaminated or their kids are infected with deadly pathogens.

E-cigarettes: new gateway to teen smoking

electronic cigarettesYoung people across the United States who smoke electronic cigarettes are considerably more likely to start smoking traditional cigarettes within a year than their peers who do not smoke e-cigarettes, according to an analysis led by the Center for Research on Media, Technology and Health (CRMTH) and the Dartmouth-Hitchcock Norris Cotton Cancer Center. The study was the first to assess this relation in a national U.S. sample of youth, and to include people older than 18 among its participants.

The results, published in JAMA Pediatrics, are particularly timely as the U.S. Food and Drug Administration considers how to regulate e-cigarettes, which are easier for adolescents to purchase and, in many respects, more attractive to young people than traditional cigarettes.

Said lead author Brian A. Primack, CRMTH director and assistant vice chancellor for health and society in the Schools of the Health Sciences: “E-cigarettes are not subject to many laws that regulate traditional cigarettes, such as age limits on sales, taxation and labeling requirements. They also come in youth-oriented flavorings that laws have limited in traditional cigarettes, such as apple bubble gum and chocolate candy cane.”
The study authors also note that electronic cigarettes are marketed on television — the first time in more than 40 years that a smoking-related device has been advertised on this medium — which has tremendous reach and could drive appeal of these products among youth.

For the current publication, the research team analyzed data on a national sample of nearly 700 nonsmokers ages 16-26 who were surveyed in 2012 and again in 2013 through the Dartmouth media, advertising and health study. Though some of those surveyed smoked e-cigarettes, all participants were considered nonsusceptible to initiating traditional cigarette smoking at the beginning of the study because they had responded “definitely no” when asked if they would try a cigarette offered by a friend or believed they would smoke a cigarette within the next year.

By the next year, 38 percent of the baseline e-cigarette users had initiated traditional cigarette smoking. In comparison, only 10 percent of the youths who were not baseline e-cigarette users started smoking traditional cigarettes.

“These differences remained statistically significant and robust even when we controlled for multiple known risk factors for initiating cigarette smoking, such as age, sex, race, ethnicity, socioeconomic status, sensation seeking, parental smoking and friend smoking,” Primack said.

In the manuscript, the research team theorize why e-cigarette smoking may serve as a gateway to traditional cigarette smoking, including:

• E-cigarettes deliver nicotine more slowly than traditional cigarettes, allowing a new user to advance to cigarette smoking as he or she becomes tolerant of nicotine side effects.

• Unlike other forms of nicotine, such as smokeless tobacco, e-cigarettes are designed to mimic the behavioral and sensory act of cigarette smoking, allowing the user to become accustomed to the act of smoking.

• E-cigarettes are not subject to the same regulations as traditional cigarettes, potentially renormalizing the act of smoking after decades of public health efforts to shift public norms around smoking.

Regulating e-cigarettes is particularly controversial because they are sometimes used as harm-reduction tools by established smokers.

However, the team adds, recent data suggest that more youth than ever are using e-cigarettes and that as many half of these adolescents are not smoking traditional cigarettes. Thus, researchers believe it is important to continue surveillance of both e-cigarettes and tobacco products among young people so that policymakers can establish research-informed regulations to help prevent e-cigarettes from becoming gateway products to youth smoking.

Additional authors on this research were Pitt’s Michael J. Fine, and colleagues from Dartmouth Institute for Health Policy and Clinical Practice and the University of Oregon.

The research was supported by the National Cancer Institute and National Center for Advancing Translational Sciences.

Evolution uses old triggers for new structures

How did the elephant get its trunk? Or the turtle its shell? How, in general, did the seemingly infinite diversity of complex animal forms on our planet arise? The scientific pursuit of how such evolutionary novelties come about is one of the big mysteries that biologists are trying to tease apart.

Mark Rebeiz, faculty member in evolutionary development in the Dietrich school’s Department of Biological Sciences, and colleagues provide some answers in a paper published in Developmental Cell.

Even in the most complex organisms, the genetic repertoire is limited. If creatures don’t evolve by acquiring new genes, how do new anatomical structures arise? Physical structures such as organs and limbs are encoded during development through the actions of collections of genes that work together in networks. Connections between genes in these networks take form primarily via gene products binding and controlling gene activation at regulatory sequences known as switches. These switches function as a blueprint for how to build an organism. They represent information that can be exploited to understand a network’s evolutionary beginnings.

Rebeiz used these switches to uncover the origins of a recently evolved structure called the posterior lobe, part of the genitalia of a certain kind of male fruit fly. Other fruit flies lack these lobes, making it a simple test system to study how an anatomical structure originated.

How does a particular structure, and its network, originate without the evolution of new genes? The answer is to reuse, or co-opt a network that was already being used at another time and place during development.

Rebeiz and colleagues found that a switch that activates a critical factor of the posterior lobe’s network could be traced to another network active during an earlier life stage. This led his team to find that several genes of the network that makes the posterior spiracle, a structure that connects the larval breathing system to the outside world, were redeployed during genital development through their posterior spiracle switches.

Said Rebeiz: “How do you make something completely new?” The answer, it seems, is to use something old. “By tracing the evolution of a network’s switches, we can see how new structures are built from networks we never would have imagined to be related.”

NIH’s $18 million will continue radiation studies

The University of Pittsburgh Cancer Institute, School of Medicine and Graduate School of Public Health have received a five-year, $18 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health to continue developing drugs that could provide protection from radiation in emergencies such as  terrorism or reactor meltdowns.

This is the third renewal of the grant for Joel S. Greenberger, chair of the Department of Radiation Oncology, and his team of researchers with the Center for Medical Countermeasures Against Radiation (CMCR). It is one of only four such grants awarded by NIAID in the U.S.

In its first 10 years, the CMCR has developed and patented two drugs to mitigate the effects of radiation on the body.Now the team will be looking at ways to administer these drugs individually or in combination using microneedle arrays. Also, they will be working to develop new drugs based on the concept of radiation-triggered disease rather than acute injury. New research will explore the molecular mechanisms through which radiation disease affects normal cells, including stem cells of the intestine and bone marrow. The frontier “omics” approaches, including oxidative lipidomics, will be employed for finding the optimal therapy regimens.

Said Greenberger: “Patients suffering from radiation disease may be too sick to take an oral therapy and delivering drugs intravenously would be too impractical and costly.”

The group’s work has gone beyond just preparing for a large-scale emergency. Some of the drugs they developed can mitigate the effects of radiation for some head and neck cancer patients.
The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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