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Archive - Oct 26, 2011

Study Examines Compensatory Up-Regulation of X Chromosome

In a study published online on October 23, 2011 in the journal Nature Genetics, a group of scientists including University of North Carolina (UNC) biologist Dr. Jason Lieb, present experiments supporting a longstanding hypothesis that explains how males can survive with only one copy of the X chromosome. The finding provides clarity to a hotly debated topic in science and provides biologists with more information to interpret experiments involving genetic measurements in males and females. "The issue is important because many diseases are tied to a defect in a regulatory mechanism within the cell," said Dr. Lieb, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Women have two X chromosomes, while men have one X and one Y. The lack of a “back up” copy of the X chromosome in males contributes to many disorders that have long been observed to occur more often in males, such as hemophilia, Duchene muscular dystrophy, and certain types of color blindness. Having only one copy of X and two copies of every other chromosome also creates a more fundamental problem – with any other chromosome, the gene number imbalance resulting from having only one copy would be lethal. How can males survive with only one X? Biologists have been debating how organisms and cells manage the imbalance between X and other chromosomes for years, with the dominant theory being that both sexes up-regulate the expression of X-linked genes, essentially doubling their expression to "2X" in males and "4X" in females. Then, to correct the imbalance that now appears in females (because they have the equivalent of "4" Xs now and 2 of every other chromosome), females then 'turn off' one of the hyperactive X chromosomes, resulting in a balanced "2X" expression of those genes across both sexes.

Exome Sequencing Reveals Mutation Associated with Hearing Impairment

Researchers have used the power of next-generation sequencing to identify a gene involved in hearing impairment in a mouse study. The findings reveal a new and unexpected function for a previously well-studied gene. The study, published on September 21, 2011 in Genome Biology, found that this mutation is involved in otitis media, an inflammation of the middle ear, which is a prominent cause of hearing impairment especially in children. This research highlights the power of genome sequencing to identify causative mutations. "Otitis media is the leading cause of surgery in children in the developed world. It affects 35% of children under the age of 2 in Europe," explains Dr. Jennifer Hilton, from the Wellcome Trust Sanger Institute and first author on the paper. "With these expanding developments in the genetics and the understanding of otitis media, there is a possibility of reducing the need for invasive surgery in young children in the future." This research emphasizes two important concepts. Firstly, exome sequencing can detect mutations that increase the chances of developing a disease but don't necessarily cause the problem in every person carrying the mutation (a phenomenon known as reduced penetrance). Secondly, the middle ear disease was detected only because the researchers looked for it, and could easily be missed in a mouse, suggesting that we only find what we look for in mouse models of disease. The team studied the exome sequence of one affected mouse and found a mutation in the Islet1 gene. They then looked for this mutation in a collection of affected mice and found that all contained the mutation in the Islet1 gene. The mutants show a thickened and inflamed lining of the middle ear and excessive fluid and cell debris in what should be an air-filled middle ear cavity, which is a clear indication of chronic otitis media.

Imperial Woodpecker Takes Flight in Recovered Film

It was once the undisputed king of its clan, but most believe the imperial woodpecker faded unseen into the pages of history sometime in the late 20th century in the high mountains of Mexico. But now, thanks to some keen detective work, the largest woodpecker that ever lived can be seen by the world once more – and this 85-second flight through time offers us a lesson about its behavior, and ours. "It is stunning to look back through time with this film and see the magnificent imperial woodpecker moving through its old-growth forest environment,” said research associate Dr. Martjan Lammertink, lead author of a paper describing the detective work, written along with four Cornell Lab of Ornithology staff members and two Mexican biologists. "And it is heartbreaking to know that both the bird and the forest are gone." The imperial woodpecker was thought to have gone extinct without anyone ever capturing photos or film of the 2-foot-tall, flamboyantly crested bird. That was until a biologist from the Cornell Lab of Ornithology tracked down a 16-mm film shot in 1956 by a dentist from Pennsylvania. The footage, which captures the last confirmed sighting of an imperial woodpecker in the wild, is available for viewing at In the color film, a female imperial woodpecker hitches up and forages on the trunks of large Durango pines and then launches into flight. The film was shot by William Rhein with a hand-held camera from the back of a mule while camping in a remote location in the Sierra Madre Occidental in Durango state. In March 2010, Dr. Lammertink and Dr. Tim Gallagher of the Cornell Lab launched an expedition with members of the conservation group Pronatura Noroeste to identify and survey the film site.

Lab-Made Skin Cells May Aid Transplantation, Cancer, and Drug Discovery Research

The pigmented cells called melanocytes aren't just for making freckles and tans. Melanocytes absorb ultraviolet light, protecting the skin from the harmful effects of the sun. They also are the cells that go haywire in melanoma, as well as in more common conditions such as vitiligo and albinism. Naturally, researchers would love to study melanocytes in the laboratory. There's just one problem -- melanocytes from adult skin do not grow very well in the lab. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have found a way to create melanocytes from mouse tail cells using embryonic stem cell-like intermediates called inducible pluripotent stem (iPS) cells. Dr. Xiaowei Xu, associate professor of Pathology and Laboratory Medicine, is senior author of the study, which was published online on August 11, 2011 in the Journal of Investigative Dermatology, ahead of the December print issue. Dr. Xu and his team converted mouse tail-tip fibroblasts into iPS cells using four genes, which were first described by Dr. Shinya Yamanaka in 2006, producing pluripotent cells similar to embryonic stem cells, but without the concomitant ethical issues. According to Dr. Xu, these lab-made melanocytes promise benefits in areas from tissue transplantation to drug discovery. "This method really has lots of clinical implications," says Dr. Xu. "We are not quite there yet, but this is an early step." For example, by collecting a tissue sample from patients with, say, vitiligo, and converting the sample to iPS cells, researchers can study what goes wrong as those cells differentiate into melanocytes--or, they can study the development and possible treatment of melanoma. Dr. Xu's new study is the first to report creating melanocytes from iPS cells in mice, and builds on his previous work. Dr.

Advance Toward Simple Breath Test for Multiple Sclerosis

Scientists from Israel, together with collaborators, are reporting the development and successful tests in humans of a sensor array that can diagnose multiple sclerosis (MS) from exhaled breath, an advance that the researchers describe as a landmark in the long search for a fast, inexpensive, and non-invasive test for MS -- the most common neurological disease in young adults. The report was published online on September 22, 2011 in the journal ACS Chemical Neuroscience. In the article, senior author Dr. Hossam Haick and colleagues report that doctors now diagnose MS based on its characteristic symptoms, which include muscle spasms, numbness, coordination problems, and slurred speech. One common tool for confirming the diagnosis and making informed decisions on treatment is magnetic resonance imaging (MRI) of the brain. Another tool is a lumbar puncture or "spinal tap" to analyze the fluid that bathes the brain and spinal cord. MRI scans, however, are costly, and lumbar punctures are invasive. To overcome these obstacles, the researchers have identified volatile organic compounds from exhaled breath that can be associated with MS. Based on these findings, the researchers developed a new sensor array that can diagnose MS by analyzing the determined chemical compounds that appear in the breath of MS patients. Using the sensors, the researchers carried out a proof-of-concept clinical study on 34 MS patients and 17 healthy volunteers and found that the sensors are just as accurate as a spinal tap, but without the pain or the risk of side effects. "The results presented here open new frontiers in the development of fast, noninvasive, and inexpensive medical diagnosis tools for detection of chronic neurological diseases," the scientists stated.

Nature Study Identifies Genetic Basis of Human Metabolic Individuality

In what is so far the largest investigation of its kind, researchers have uncovered a wide range of new insights about common diseases and how they are affected by differences between two persons' genes. The results from this study could lead to highly targeted, individualized therapies. Led by researchers from Weill Cornell Medical College-Qatar and published in the September 1, 2011 issue of Nature, the study provides details on the genetics behind many diseases, including cardiovascular and kidney disorders, diabetes, cancer, gout, thrombosis, and Crohn's disease, and elucidates the role that individual differences in metabolism play in these disorders. Disturbances in metabolism are at the root of a variety of human afflictions and complex diseases. Although many of the genes that contribute to these conditions have been identified since the completion of the Human Genome Project in 2003, it is still not known how metabolic disorders related to these genetic aberrations disrupt cellular processes. One hundred years ago, Dr. Archibald Garrod, one of the fathers of modern biochemistry, realized that inborn errors in human metabolism are "merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees" and that this "chemical individuality [confers] predisposition to and immunities from the various mishaps which are spoken of as diseases." Ever since, identification of the genetic basis of human chemical individuality has been elusive. Now researchers have addressed this challenge by using a new technology, called metabolomics. They measured the levels of more than 250 biochemical compounds in over 60 metabolic pathways, including lipids, sugars, vitamins, amino acids and others in blood from over 2,800 individuals.