On November 11, 1954, Dr. Syuiti Mori turned out the lights on a small group of fruit flies. More than sixty years later, the descendents of those flies have adapted to life without light. The flies, a Drosophila melanogaster variety now known as "Dark-fly,” out-compete their light-loving wild-type cousins when they live together in constant darkness, according to research reported in the February 2016 issue of the open-access journal G3: Genes|Genomes|Genetics, published by the Genetics Society of America. This competitive difference allowed the researchers to re-play the evolution of Dark-Fly and identify the genomic regions that contribute to its success in the dark. The G3 article is titled “Dynamics of Dark-Fly Genome Under Environmental Selections” and it served as the cover story of the February issue of the journal. "We hope understanding the genetics behind Dark-Fly's adaptations will shed light on how genes are selected during rapid evolution," says study leader Naoyuki Fuse, Ph.D., of Kyoto University in Japan. The Dark-Fly project is the longest-running example of an experimental evolution study where scientists follow a population over many generations. It is also the first to analyze genome evolution in a multi-cellular organism adapted to a defined condition in the lab. The project was initiated by Dr. Mori as part of a series of experiments investigating how the traits of fruit flies are altered in response to changes in their environment. The fruit fly Drosophila melanogaster is a heavily studied model organism often used to examine genetic changes during evolution. To keep the flies away from light, they are reared in vials kept in a large pot painted black on the inside and covered with a blackout cloth.
Two years ago, Ellen Martinsen, Ph.D., was collecting mosquitoes at the Smithsonian's National Zoo in Washingon, DC, looking for malaria parasites that might infect birds, when she discovered something strange: a DNA profile, from parasites in the mosquitoes, that she couldn't identify. By chance, she had discovered a malaria parasite, Plasmodium odocoilei--that infects white-tailed deer. It's the first-ever malaria parasite known to live in a deer species and the only native malaria parasite found in any mammal in North or South America. Though white-tailed deer diseases have been heavily studied--scientist hadn't noticed that many have malaria parasites. Dr. Martinsen and her colleagues now estimate that the P. odocoilie parasite infects up to twenty-five percent of white-tailed deer along the East Coast of the United States. Their results were published online on February 5, 2016 in Science Advances. The article is titled “Hidden in Plain Sight: Cryptic and Endemic Malaria Parasites in North American White-Tailed Deer (Odocoileus virginianu.” “You never know what you're going to find when you're out in nature--and you look," says Dr. Martinsen, a research associate at the Smithsonian's Conservation Biology Institute and an adjunct faculty member in the University of Vermont's (UVM’s) Biology Department. "It's a parasite that has been hidden in the most iconic game animal in the United States. I just stumbled across it." The newly published study, led by Dr. Martinsen, was a collaboration among scientists at the Smithsonian Conservation Biology Institute, the American Museum of Natural History, the National Park Service, the University of Georgia, the University of Wisconsin-Milwaukee--and UVM biologist and malaria expert Joseph Schall, Ph.D. Although Dr. Martinsen and Dr.
More than 15 years ago, David Warshaw, Ph.D., and coworkers discovered the precise malfunction of a specific protein in the heart that leads to hypertrophic cardiomyopathy (HCM), a common culprit in cases of sudden death in young athletes. Now, a team of scientists has used some of Dr. Warshaw's earlier findings to develop a possible treatment to prevent HCM, an inherited disease that can cause the heart to thicken and stop pumping blood effectively, leading to heart failure. Dr. Warshaw, now Professor and Chair of Molecular Physiology and Biophysics at the University of Vermont (UVM) College of Medicine, wrote about the significance of this potential therapy in a "Perspectives" column in the February 5, 2016 issue of the journal Science. The title of this piece is “Throttling Bace the Heart’s Molecular Motor.” "This may offer a generalized approach to solving hypertrophic cardiomyopathy," says Dr. Warshaw, who is also an Investigator in the Cardiovascular Research Institute of Vermont at UVM. "I think it's extremely promising." HCM can result from different mutations of many different proteins in the heart. One of those proteins, myosin, acts as a tiny molecular motor in every heart muscle cell. Myosin pulls on and releases a rope-like protein, actin, in order to make the heart muscle contract and relax as it pumps blood. A mutation of myosin can "alter the motor's power-generating capacity" and make the heart work improperly, which in turn causes the heart to enlarge (hypertrophy), Dr. Warshaw says. For many years, scientists assumed that the mutation caused the myosin to lose its motoring power, throwing off the whole heart engine. But in a study Dr.
There may be a genetic connection between certain mental health disorders and type 2 diabetes. In a new report appearing in the February 2016 issue of The FASEB Journal, scientists show that a gene called "DISC1," which is believed to play a key role in mental health disorders, such as schizophrenia, bipolar disorder, and some forms of depression, influences the function of pancreatic beta cells which produce insulin to maintain normal blood glucose levels. The FASEB Journal article is titled “Beyond the Brain: Disrupted in Schizophrenia 1 Regulates Pancreatic β-cell Function via Glycogen Synthase Kinase-3β.” "Studies exploring the biology of disease have increasingly identified the involvement of unanticipated proteins--DISC1 fits this category," said Rita Bortell, Ph.D., a researcher involved in new work from the Diabetes Center of Excellence at the Universityof Massachusetts Medical School in Worcester, Massachusetts. "Our hope is that the association we've found linking disrupted DISC1 to both diabetes and psychiatric disorders may uncover mechanisms to improve therapies, even preventative ones, to alleviate suffering caused by both illnesses which are extraordinarily costly, very common, often quite debilitating." To make their discovery, Dr. Bortell and colleagues studied the function of DISC1 by comparing two groups of mice. The first group was genetically manipulated to disrupt the DISC1 gene only in the mouse's pancreatic beta cells. The second group of mice was normal. The mice with disrupted DISC1 gene showed increased beta cell death, less insulin secretion, and impaired glucose regulation while control mice were normal.
Chronic inflammation in the gut increases the risk of colon cancer by as much as 500 percent, and now Duke University researchers think they know why. Their new study points to a biomarker in the cellular machinery that could not only serve as an early warning of colon cancer, but potentially be harnessed to counteract advanced forms of the disease, the second-largest cause of cancer death in the U.S. In the study, published online on February 4, 2016 in the journal Cell Stem Cell, Duke biomedical engineers show how colon cancer development is intricately linked to a specific microRNA that dictates how cells divide. “A quarter of the world's population is affected by some type of gut inflammation,” said lead author Xiling Shen, Ph.D., Associate Professor of Biomedical Engineering at Duke University. "These patients always have a much higher chance of developing colon cancer, but it was never clear why. Now we have found a link.” The Cancer Stem Cell article is titled “A miR-34a-Numb Feed-Forward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer." In the study, Dr. Shen's group focused on a microRNA called miR-34a that gives cancer stem cells the odd ability to divide asymmetrically. This process controls the cancerous stem cell population and generates a diverse set of cells. While researchers knew that miR-34a is responsible for this ability, nobody knew where the ability came from, because normal, healthy colon stem cells don't asymmetrically divide and don't need this microRNA. They wondered if there was a mutation unique to cancer stem cells, or a hidden role for the microRNA in normal physiology. To find out, Dr. Shen and his colleagues deleted miR-34a from the genetic code of some mice. But nothing happened. "It really puzzled the scientific community," said Dr. Shen.
Using a special profiling technique, scientists at Princeton University have determined the mechanism of action of a potent antibiotic, known as tropodithietic acid (TDA) (image), leading them to uncover its hidden ability as a potential anti-cancer agent. TDA is produced by marine bacteria belonging to the roseobacter family, which exist in a unique symbiosis with microscopic algae. The algae provide food for the bacteria, and the bacteria provide protection from the many pathogens of the open ocean. "This molecule keeps everything out," said Mohammad Seyedsayamdost, Ph.D., an Assistant Professor of Chemistry at Princeton and corresponding author on the study published online on January 22, 2016 in PNAS. "How could something so small be so broad-spectrum? That's what got us interested," he said. The PNAS article is titled “Mode of Action and Resistance Studies Unveil New Roles for Tropodithietic Acid As an Anticancer Agent and the -Glutamyl Cycle As a Proton Sink.” In collaboration with researchers in the laboratory of Zemer Gitai, Ph.D., an Associate Professor of Molecular Biology at Princeton, the team used a laboratory technique referred to as bacterial cytological profiling to investigate the mode of action of TDA. This method involves destroying bacterial cells with the antibiotic in the presence of a set of dyes, and then visually assessing the aftermath. “The key assumption is that dead cells that look the same probably died by the same mechanism,” Dr. Seyedsayamdost said. The team used three dyes to evaluate 13 different features of the deceased cells, such as cell membrane thickness and nucleoid area, comprising TDA's cytological profile. By comparing TDA’s profile to those for other known drugs, the researchers found a match with a class of compounds called polyethers, which possess anti-cancer activity.
The brain still has a lot to learn about itself. Scientists at the Virginia Tech Carilion Research Institute have made a key finding of the striking differences in how the brain's cells can change through experience. Their results were published online on February 3, 2016 in the open-access journal PLOS ONE. The article is titled “Role of GABAA-Mediated Inhibition and Functional Assortment of Synapses onto Individual Layer 4 Neurons in Regulating Plasticity Expression in Visual Cortex.” “Neurons can undergo long-term changes in response to experience such as learning, emotions, or other activity," said Michael Friedlander, Ph.D., Executive Director of the Virginia Tech Carilion Research Institute. Dr. Friedlander co-authored the paper with his former graduate student and postdoctoral fellow, Dr. Ignacio Saez. "Neuroscientists have focused much of their attention on understanding the neuroplasticity of the connections between nerve cells called synapses," Dr. Friedlander said. Synapses, the specialized connections between neurons, work by translating an electrical signal from one neuron into a chemical signal to modify the receiving neuron. The chemical signal triggers an electrical signal in the receiving neuron, and the process continues. Synapses may become stronger or weaker by changing efficiency of the chemical communication process in response to repeated bouts of co-activation of the two interconnected neurons. This process, called synaptic plasticity, can cause changes that persist beyond the co-activation period for mere minutes through a lifetime. Outside experience can be internalized as a physical reorganization of the brain's synaptic communication process.
Head and neck cancers include a heterogeneous group of tumors located in the oral cavity, pharynx, and larynx. Despite therapeutic progress, the survival rate of patients with this pathology has hardly improved in the last decade. Many researchers are focusing on understanding the molecular biology of these tumors to improve their prognosis and treatment. “One problem is the stratification of patients, which in many cases is limited to a clinical classification, not a molecular one,” argue Dr. Susana Llanos and Dr. Juana M. García-Pedrero, authors of the study from the Tumor Suppression Group of the Spanish National Cancer Research Centre (CNIO) and from the Central University Hospital of Asturias (HUCA), respectively. These researchers have analyzed more than 270 biopsies of patients with head and neck cancers, and have found that about half of them show high levels of the p21 protein, as well as mTOR activation. This research project, directed by Dr. Manuel Serrano, Head of the Tumor Suppression Group and Director of the CNIO's Molecular Oncology Program, has found that the presence of p21 is closely linked to the activity of mTOR and that both markers predict a less aggressive evolution of the disease. In the future, patient classification based on these markers could allow physicians to choose the best therapeutic option for each group. The conclusions were published online on February 2, 2016 in an open-access article in Nature Communications. The article is titled “Stabilization of p21 by mTORC1/4E-BP1 Predicts Clinical Outcome of Head and Neck Cancers.” The researchers have also unraveled the molecular mechanism by which p21 levels are linked to the activity of mTOR. In particular, when the mTOR protein is inactive, it dictates the degradation of p21, and, conversely, when mTOR is active, p21 becomes stable.
University of California (UC) Davis researchers have developed a way to use the empty shell of a hepatitis E virus to carry vaccines or drugs into the body. The technique has been tested in rodents as a way to target breast cancer, and is available for commercial licensing through the UC Davis Office of Research. Hepatitis E virus is feco-orally transmitted, so it can survive passage through the digestive system, said Marie Stark, a graduate student working with Professor Holland Cheng in the UC Davis Department of Molecular and Cell Biology. Dr. Cheng, Ms. Stark, and colleagues prepared virus-like particles based on hepatitis E proteins. The particles do not contain any virus DNA, so they cannot multiply and spread and cause infections. Such particles could be used as vaccines that are delivered through food or drink. The idea is that you would drink the vaccine, and after passage through the stomach the virus-like particles would be absorbed in the intestine and deliver vaccines to the body. But the particles could also be used to attack cancer. Ms. Stark and Dr. Cheng did some tinkering with the proteins, so that they carry sticky cysteine amino acids on the outside. They could then chemically link other molecules to these cysteine groups. The scientists worked with a molecule called LXY-30, developed by researchers at the UC Davis Comprehensive Cancer Center, which is known to stick to breast cancer cells. By using a fluorescent marker, they could show that virus-like particles carrying LXY-30 could home in on breast cancer cells both in a laboratory dish and in a mouse model of breast cancer. Results of the study have been published online in the journal Nanomedicine. Information on licensing the technology can be found at: https://techtransfer.universityofcalifornia.edu/NCD/24218.html.
With over half the U.S. population infected, most people are familiar with the pesky cold sore outbreaks caused by the herpes simplex 1 virus. The virus outsmarts the immune system by interfering with the process that normally allows immune cells to recognize and destroy foreign invaders. How exactly the herpes simplex 1 virus pulls off its nifty scheme has long been elusive to scientists. Now, new research from The Rockefeller University sheds light on the phenomenon. A team of structural biologists in Dr. Jue Chen's Laboratory of Membrane Biology and Biophysics has captured atomic images of the virus in action, revealing how a viral protein (ICP47) is inserted into a key cellular protein to cause a traffic jam in an important immune system pathway. The findings were published online in Nature on January 20, 2016. The article is titled “A Mechanism of Viral Immune Evasion Revealed by Cryo-EM Analysis of the TAP Transporter.” "This work illustrates a striking example of how a persistent virus evades the immune system," says Dr. Chen. "Once this virus enters the body, it never leaves. Our findings provide a mechanistic explanation for how it's able to escape detection by immune cells." When a virus enters the body, it typically gets chewed up inside cells, and little pieces of the virus end up stuck to the outside of the cells. "These pieces act like a barcode to immune cells, which sense that a pathogen is present, and attack," says senior research associate and first author of the paper, Dr. Michael Oldham. One piece of the machinery involved in getting bits of virus to the cell's surface is a protein called TAP (transporter associated with antigen processing).