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Archive - Aug 2, 2014

Hearing Gene Prestin Adapted for Echolocation in Bats and Dolphins

A little over a decade ago, prestin was found to be a key gene responsible for hearing in mammals. Prestin makes a protein found in the hair cells of the inner ear that contracts and expands rapidly to transmit signals that help the cochlea, like an antique phonograph horn, amplify sound waves to make hearing more sensitivity. Now, in a new study published in the online on June 19, 2014 in Molecular Biology and Evolution, Dr. Peng Shi, et al., have shown that prestin has also independently evolved to play a critical role in the ultrasonic hearing range of animal sonar, or echolocation, to help dolphins navigate through murky waters or bats to find food in the dark. Although both toothed whales and echolocating bats can emit high frequency echolocation calls, which show a substantial diversity in terms of their shape, duration, and amplitude, they receive and analyze the echoes returned from objects by their high-frequency hearing. The research team finely dissected the function of the prestin protein from 2 sonar-guided bats and the bottlenose dolphin compared with non-sonar mammals. Evolutionary analyses of the prestin protein sequences showed that a single amino acid change in prestin, from a threonine (Thr or T) in all sonar mammals to an asparagine (Asn or N) in all non-sonar mammals, was subject to parallel evolution, suggesting that it may play a critical role for mammalian echolocation. Further experiments supported this assumption and identified 4 key amino acid differences amongst the sonar mammals, which may contribute to their unique features . Taken along side evolutionary analyses, these findings offered the first functional evidence supporting the notion that the hearing gene of prestin evolved to play a key role in the sonar system of mammals.

New Molecular Test Kit Predicts Patient’s Survival and Drug Response in Kidney Cancer

Researchers and doctors at the Institute of Bioengineering and Nanotechnology (IBN), Singapore General Hospital (SGH) and National Cancer Centre Singapore (NCCS) have co-developed the first molecular test kit that can predict treatment and survival outcomes in kidney cancer patients. This breakthrough was reported online on July 17, 2014 in European Urology, the world’s top urology journal. According to IBN Executive Director Professor Jackie Y. Ying, “By combining our expertise in molecular diagnostics and cancer research, we have developed the first genetic test to help doctors prescribe the appropriate treatment for kidney cancer patients based on their tumor profile.” Dr. Min-Han Tan, who is IBN Team Leader and Principal Research Scientist and a visiting consultant at the Division of Medical Oncology NCCS, shared his motivation, “As a practicing oncologist, I have cared for many patients with kidney cancer. I see the high costs of cancer care, the unpredictable outcomes, and occasional futility of even the best available drugs. This experience inspired our development of this assay to improve all these for patients.” The study was conducted retrospectively with tissue samples collected from close to 280 clear cell renal cell carcinoma (ccRCC) patients who underwent surgery at SGH between 1999 and 2012. “High-quality tissue samples are crucial in achieving significant findings in biomedical research. As an Academic Medical Center, we wish to promote the translation of research into advances in healthcare and personalized medicine. The development of this test kit for patient care, utilizing the robust tissue archive that we have at SGH, is a good example of this,” said Professor Tan Puay Hoon, Head and Senior Consultant, Department of Pathology, SGH.

Switching on Brown Fat Thermogenesis

Biologists at The Scripps Research Institute (TSRI) in La Jolla, California, have identified a signaling pathway that switches on a powerful calorie-burning process in brown fat cells. The study, which was reported online on July 28, 2014 in PNAS, sheds light on a process known as "brown fat thermogenesis," which is of great interest to medical researchers because it naturally stimulates weight loss and may also protect against diabetes. "This finding offers new possibilities for the therapeutic activation of brown fat thermogenesis," said team leader Dr. Anastasia Kralli, associate professor in TSRI's Departments of Chemical Physiology and Cell Biology. Most fat cells in our bodies are "white fat" cells that store fat as a reserve energy supply. But we and other mammals also have depots of "brown fat" cells. These apparently evolved not to store but to burn energy—quickly, as a way of generating heat and keeping the body warm in cold conditions, as well as possibly to get rid of excess caloric intake. Human babies as well as mammals that hibernate have relatively extensive brown fat tissues. Scientists have found in recent years that many adult humans have significant levels of brown fat, which are located mostly in the neck and shoulders, and appear to help regulate body weight and blood sugar. Low temperatures activate the brown-fat thermogenesis process via the sympathetic nervous system: Nerve ends in brown fat tissue release the neurotransmitter norepinephrine, and that triggers a shift in metabolism within the brown fat cells, which are densely packed with tiny biological energy reactors called mitochondria. "The mitochondria start generating heat instead of useful chemical energy; it's like revving the engines of a lot of parked cars," said first author Dr.

Sustained Efficacy, Immunogenicity, and Safety Shown for GlaxoSmithKline's HPV Vaccine

A long-term follow-up study (HPV-023; NCT00518336) shows the sustained efficacy, immunogenicity, and safety of GlaxoSmithKline's human papilloma virus (HPV) vaccine Cervarix. Women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine were followed for more than nine years, and vaccine efficacy (VE) against incident infection was 100%. This is the longest follow-up report for a licensed HPV vaccine. Visit https://www.landesbioscience.com/journals/vaccines/article/29532/ for the full paper. The article was published on June 19, 2014 in Human Vaccines & Immunotherapeutics. Persistent infection with HPV has been clearly established as the necessary cause of the overwhelming majority of cervical cancer cases. At least 40 different HPV types are known to infect the genital mucosa, of which approximately 15 are associated with cervical cancer. Among these types, HPV-16 and HPV-18 are the most common and responsible for approximately 70% of cervical cancers. Both HPV-16 and HPV-18 are included in the two licensed HPV vaccines (GSK's Cervarix and Merck's Gardasil), which are now widely available and used. Evidence of long-term efficacy against vaccine HPV-types is very important, particularly with respect to maintaining public confidence in mass vaccination programs. HPV vaccines initially were recommended for young girls and women 9-25 years of age who have not been exposed to HPV. Because HPV causes not only cervical cancer but also genital warts and anal cancer, HPV vaccines are also recommended for boys in many countries. An initial double-blind, randomized, multi-center vaccination study (HPV-001; NCT00689741) was started in 2001, followed for up to 27 months, and then followed by a long-term study of the entire cohort for up to 77 months (6,4 years) post initial vaccination (HPV-007; NCT00120848).

Twin Study Reveals Altered Gene for Short Sleep Requirement and More Rapid Recovery from Lost Sleep

Researchers who studied 100 twin pairs (dizygotic and monozygotic) have identified a gene mutation that may allow the carrier to function normally on less than six hours of sleep per night. The genetic variant also appears to provide greater resistance to the effects of sleep deprivation. Results show that a participant with p.Tyr362His – a variant of the BHLHE41 gene – had an average nightly sleep duration of only five hours, which was more than one hour shorter than the non-carrier twin, who slept for about six hours and five minutes per night. The twin with the gene mutation also had 40 percent fewer average lapses of performance during 38 hours without sleep and required less recovery sleep afterward – sleeping only eight hours after the period of extended sleep deprivation compared with his twin brother, who slept for 9.5 hours. According to the authors, this is only the second study to link a mutation of the BHLHE41 gene – also known as DEC2 - to short sleep duration. The study provides new insights into the genetic basis of short sleep in humans and the molecular mechanisms involved in setting the duration of sleep that individuals need. “This work provides an important second gene variant associated with sleep deprivation and for the first time shows the role of BHLHE41 in resistance to sleep deprivation in humans,” said lead author Renata Pellegrino, Ph.D., senior research associate in the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “The mutation was associated with resistance to the neurobehavioral effects of sleep deprivation.” Study results are published in the August 1, 2014 issue of the journal Sleep. The study group comprised 100 twin pairs – 59 monozygotic pairs and 41 dizygotic pairs – who were recruited at the University of Pennsylvania.