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April 15, 2015

In Research

A novel way to attack dental plaque

graphic of nanoparticle tangles carrying chemical to tooth surfaces
An antibacterial agent called Farnesol is released from nanoparticle carriers into cavity-causing dental plaque. Researchers hope their findings will someday lead to better treatments for plaque and tooth decay.

A team of researchers, led by Rochester’s Danielle Benoit and Hyun Koo at the University of Pennsylvania’s School of Dental Medicine, has developed a way to keep drugs intended to prevent tooth decay from being washed away by saliva before they can take effect.

Their findings were published in the journal ACS Nano.

“We had two specific challenges,” says Benoit, the James P. Wilmot Distinguished Assistant Professor of Biomedical Engineering. “We had to figure out how to deliver the antibacterial agent to the teeth and keep it there and also how to release the agent into the targeted sites.”

To deliver the agent—known as Farnesol—the researchers created a spherical mass of particles, referred to as a nanoparticle carrier. They constructed the outer layer out of cationic—or positively charged—segments of the polymers. For inside the carrier, they secured the drug with hydrophobic and pH-responsive polymers.

The positively charged outer layer of the carrier is able to stay in place at the surface of the teeth because the enamel is made up, in part, of HA (hydroxyapatite), which is negatively charged. Just as oppositely charged magnets are attracted to each other, the same is true of the nanoparticles and HA. Because teeth are coated with saliva, the researchers weren’t certain the nanoparticles would adhere. But not only did the particles stay in place, they were also able to bind with the polymeric matrix and stick to dental plaque.

The researchers hope their results will lead to better—and perhaps permanent—treatments for dental plaque and tooth decay, as well as other biofilm-related diseases.


Study finds new genetic clues to pediatric seizures

Researchers have identified a new genetic mutation at the heart of a severe and potentially deadly seizure disorder found in infants and young children. The finding, which was reported in American Journal of Human Genetics, may help scientists unravel the complex biological mechanism behind the diseases.

“These findings allow us to open up what was, up to this point, a ‘black box’ and more fully understand the biological pathways associated with these disorders and why some individuals do not respond to treatment,” says Alex Paciorkowski, assistant professor of neurology and lead author of the study.

The study focuses on a severe form of seizure disorders collectively referred to as developmental epilepsies.

The researchers analyzed the genetic profiles of 101 children with developmental epilepsy and were able to identify a mutation in a gene called salt-inducible kinase 1 (SIK1), a gene previously unidentified with the disease and one which the researchers believe plays a role in a chain reaction of gene and protein interactions in neurons that contribute to seizures.

The link between the SIK1 mutation and developmental epilepsy was made possible through the intersection of genetics, neurobiology, and high performance computing. The researchers utilized a supercomputer cluster at the University to sift through enormous sets of genetic information quickly and efficiently.

The primary drug used to treat developmental epilepsy is adrenocorticotropic hormone (ACTH). However, the drug has life-threatening side effects, is expensive, and is ineffective in about 40 percent of cases. The new finding may enable researchers to better identify who would be likely to benefit from the treatment.


Low vitamin D linked to worse prognosis in type of lymphoma

A new study indicates that people with lower vitamin D levels prior to treatment for follicular lymphoma succumb to the disease or face relapse earlier than patients with sufficient vitamin D levels in their blood.

The Wilmot Cancer Institute investigation is believed to be the first to report that lack of vitamin D is a potentially modifiable risk factor for this type of cancer. The study was published by the Journal of Clinical Oncology.

Jonathan Friedberg, director of the Wilmot Cancer Institute, and Jennifer Kelly, an epidemiologist at the School of Medicine and Dentistry, led the collaborative follicular lymphoma study between SWOG, a component of the NCI-sponsored National Clinical Trials Network, and the Lymphoma Study Association, based in France.

Researchers observed a total of 423 follicular lymphoma patients in two independent cohorts who were followed for a minimum of five and a half years each. They measured the patients’ baseline vitamin D blood levels before cancer treatment began and then tracked and analyzed cancer survival data for each group.

Vitamin D’s connection to cancer is an active research topic. Prior studies have shown a survival benefit among patients with higher vitamin D levels for diffuse large B-cell lymphoma and chronic lymphocytic leukemia. In addition, earlier peer-reviewed research at Wilmot showed that low vitamin D levels among women with breast cancer correlated with more aggressive tumors and poorer prognosis, and that vitamin D deficiency among African Americans might help to explain higher death rates from colorectal cancer. Currently, Wilmot investigators are evaluating whether high weekly doses of vitamin D (50,000 IU) improves the side effects related to androgen deprivation therapy for prostate cancer in patients ages 65 and older.


Do brands care about your social media popularity?

Social media has transformed customer service as consumers seek immediate responses from companies through social media outlets. So, how do companies choose which complaints or compliments get a response? The answer may lie in the consumer’s social media popularity, according to new research from the Simon Business School.

After examining Twitter data from major U.S. airlines, researchers found that companies are more likely to engage with customers who have a high number of followers.
“Twitter users with a large number of followers are better poised to influence other users with their perceptions of a brand,” says coauthor Huaxia Rui, assistant professor of computers and information systems at Simon. “Knowing these users can be highly influential, brands will have more incentive to allocate their resources prioritizing response for those they view as influential customers, thus minimizing risk and halting a potential social media crisis.”

The research is based on a large sample of tweets mentioning the official accounts of these airlines in 2014 and reply tweets by the airlines. Researchers divided the tweets sent to the airlines into three categories: complaints, compliments, or neutral tweet in order to discover what type of tweets were more likely to garner a response from the airlines.


Work-based wellness programs reduce weight

A new study indicates that workplace wellness programs can be effective in helping people lose weight by providing healthier food choices and increasing opportunities for physical activity, particularly if these efforts are designed with the input and active participation of employees.

The two-year project—the results of which appear in the American Journal of Public Health—successfully reduced the number of people considered overweight or obese by almost 9 percent.

“Worksites are self-contained environments with established communication systems where interventions that modify food options and provide physical activity have the potential to reach large numbers of adults,” says Diana Fernandez, associate professor of public health sciences and lead author of the study. “This study shows in particular that when employees are empowered to help shape wellness programs, these programs appear to result in meaningful improvements in health.”

The researchers worked with a Rochester-based company with sites throughout the northeastern United States. Ten different sites were randomized into two groups, and the study examined a total of 3,799 individuals. The researchers worked with management and employees in the intervention group to establish workplace programs that focused on healthy eating and increasing physical activity. The control group did not receive any intervention.

At the end of the study period, the number of employees in the control site who were overweight or obese increased by about 5 percent, while the number in the intervention group had decreased by 4 percent resulting in a net difference of 9 percent.

“This study suggests that worksite environmental interventions might be promising strategies for weight control at the population level,” says Fernandez. “These observations lend support to the approaches that might eventually reduce the incidence and prevalence of overweight and obesity on a larger scale.”


Blocking cell mechanism gives chemotherapy a boost

A Rochester team found a way to make chemotherapy more effective—by stopping a cellular quality-control mechanism.

The mechanism is known as NMD (nonsense-mediated mRNA decay), and scientists found that exposing breast cancer cells to a molecule that inhibits NMD prior to treatment with doxorubicin, a drug used to treat leukemia, breast, bone, lung and other cancers, hastens cell death.

The study was published in Nature Communications.

The research team, led by Lynne Maquat, director of the Center for RNA Biology, says that the work is in the early stages and a long way from being applied in humans. But, they believe their data provide insights that could lead to new treatment strategies for cancer patients in the future.

Maximilian Popp, study author and a postdoctoral fellow in Maquat’s laboratory, describes NMD as the body’s way of proofreading messenger RNA or mRNA, which takes genetic instructions from DNA and uses it to create proteins that carry out the body’s functions. NMD flags and derails the production of unwanted proteins that can disrupt normal processes and initiate disease, like an inspector flags and removes faulty products from an assembly line.

In the last several years, Maquat’s team and others have discovered that NMD is a more dynamic pathway than they thought; it also helps our cells adjust to changes in their environment and more rapidly respond to certain stimuli.

“This research highlights the importance of basic research and its relevance to human disease and therapies,” says Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in the Department of Biochemistry and Biophysics.


‘Twisted light’ improves efficiency of quantum cryptography systems

Rochester researchers and their collaborators have developed a way to transfer 2.05 bits per photon by using “twisted light.”

The researchers used the orbital angular momentum of the photons rather than the more commonly used polarization of light to encode information. The new approach doubles the 1 bit per photon that is possible with current systems that rely on light polarization and could help increase the efficiency of quantum cryptography systems.

Quantum cryptography promises more secure communications. The first step in such systems is quantum key distribution, to ensure that both the sender and receiver—usually referred to as Alice and Bob—are communicating in such a way that only they know what is being sent. They are the only ones who hold the “key” to the messages, and the systems are set up in such a way that the presence of any eavesdropper would be identified.

In the paper, published in New Journal of Physics, Mohammad Mirhosseini and his colleagues describe a proof-of-principle experiment that shows that using orbital angular momentum to encode information rather than polarization opens up the possibility of high-dimensional quantum key distribution. Mirhosseini, a PhD student in Robert Boyd’s group at the Institute of Optics, says that they were able to encode a seven-dimensional

“alphabet”—seven letters or symbols—using both the orbital angular momentum of the photons and their angular position. The two properties of the photons form what physicists refer to as mutually unbiased bases, a requirement for quantum key distribution. Using mutually unbiased bases, the correct answer is revealed only if Alice encodes the information using a particular basis and Bob measures in that same basis.

The researchers showed that using their system, they were able to generate and detect information at a rate of 4kHz and with 93 percent accuracy. A long-term goal of the research is to realize secure communications at GHz transmission rates, a desirable trait for telecommunication applications.

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