The principle of adaptation--the gradual modification of a species' structures and features--is one of the pillars of evolution. While there exists ample evidence to support the slow, ongoing process that alters the genetic makeup of a species, scientists could only suspect that there were also organisms capable of transforming themselves ad hoc to adjust to changing conditions. Now, a new study published online on January 8, 2015 in eLife by Dr. Eli Eisenberg of Tel Aviv University's (TAU’s) Department of Physics and Sagol School of Neuroscience, in collaboration with Dr. Joshua J. Rosenthal of the University of Puerto Rico, showcases the first example of an animal editing its own genetic makeup on-the-fly to modify most of its proteins, enabling adjustments to its immediate surroundings. The article is titled “The Majority of Transcripts in the Squid Nervous System Are Extensively Recoded by A-to-I RNA Editing.” The research, conducted in part by TAU graduate student Shahar Alon, explored RNA editing in the Doryteuthis pealieii squid. "We have demonstrated that RNA editing is a major player in genetic information processing, rather than an exception to the rule," said Dr. Eisenberg. "By showing that the squid's RNA editing dramatically reshaped its entire proteome — the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time — we proved that an organism’s self-editing of mRNA is a critical evolutionary and adaptive force." This demonstration, he said, may have implications for human diseases as well. RNA is a copy of the genetic code that is translated into protein. But the RNA "transcript" can be edited before being translated into protein, paving the way for different versions of proteins. Abnormal RNA editing in humans has been observed in patients with neurological diseases.
Schizophrenia is not only associated with positive symptoms such as hallucinations and delusions, but also with negative symptoms e.g., cognitive deficits and impairments of the emotional drive. Until now, the underlying mechanisms for these negative symptoms have not been well characterized. In an article published online on February 9, 2015 in PNAS, a German-American team of researchers, with the cooperation of the Goethe University, reports that a selective dopamine midbrain neuron population that is crucial for emotional and cognitive processing shows reduced electrical in vivo activity in a disease mouse model. The title of the PNAS article is “Increased Dopamine D2 Receptor Activity in the Striatum Alters the Firing Pattern of Dopamine Neurons in the Ventral Tegmental Area.” ”Schizophrenia is a severe and incurable psychiatric illness, which affects approximately one percent of the world population. While acute psychotic states of the disease have been successfully treated with psycho-pharmaceutical drugs (anti-psychotic agents) for many decades, cognitive deficits and impairments of motivation do not respond well to standard drug therapy. This is a crucial problem, as the long-term prognosis of a patient is determined above all by the severity of these negative symptoms. Therefore, the shortened average life-span of about 25 years for schizophrenia patients remained largely unaltered in recent decades. "In order to develop new therapy strategies, we need an improved neurobiological understanding of the negative symptoms of schizophrenia" explains Professor Jochen Roeper of the Institute for Neurophysiology of the Goethe University.
Allowing dingoes to return to Sturt National Park in New South Wales, Australia and researching the results may be the key to managing the future of dingoes and many threatened native mammals, University of Sydney researchers believe. "Our approach is purposefully bold because only an experiment on this scale can resolve the long-running debate over whether the dingo can help halt Australia's biodiversity collapse and restore degraded rangeland environments," said Dr. Thomas Newsome from the School of Biological Sciences at the University of Sydney and lead author of an article published February 16, 2015 in Restoration Ecology. Written with Dr. Newsome's colleagues from the University of Sydney and other universities in Australia, and in America, where Dr. Newsome completed a Fulbright Scholarship, the article outlines how the experiment could be undertaken. "Half the world's mammal extinctions over the last two hundred years have occurred in Australia and we are on track for an acceleration of that loss. This experiment would provide robust data to address an issue of national and international significance," said Dr. Newsome. "Our approach is based on dingoes' ability to suppress populations of invasive predators such as red foxes and feral cats that prey on threatened native species. Dingoes can also control numbers of introduced species such as European wild rabbits, feral pigs, and goats or native herbivores such as kangaroos, that in high numbers can contribute to rangeland degradation. "There are major challenges, including convincing livestock producers and local communities to support the experiment, but we currently have almost no understanding of the impact of increased dingo populations over large areas.
A new study suggests that bacteria may be able to jump between host species far more easily than was previously thought. Researchers have discovered that a single genetic mutation in a strain of bacteria infectious to humans enables it to jump species to also become infectious to rabbits. The discovery has major implications for how we assess the risk of bacterial diseases that can pass between humans and animals. It is well known that relatively few mutations are required to support the transmission of viruses, such as influenza, from one species to another. Until now, it was thought that the process was likely to be far more complicated for bacteria. The new study was published online on February 16, 2015 in Nature Genetics. The title of the article was “A Single Natural Nucleotide Mutation Alters Bacterial Pathogen Host Tropism.” Scientists at the Universities of CEU Cardenal Herrera (Spain), and of Glasgow (UK), and of Edinburgh (UK) studied a strain of bacteria called Staphylococcus aureus ST121, which is responsible for widespread epidemics of disease in the global rabbit farming industry. The team looked at the genetic make-up of S. aureus ST121 to work out where the strain originated and the changes that occurred that enabled it to infect rabbits. The scientists found that S. aureus ST121 most likely evolved through a host jump from humans to rabbits approximately 40 years ago, with a genetic mutation at a single site in the bacterial DNA code being the cause for this.
Investigators with the National Institutes of Health (NIH) have discovered the genomic switches of a blood cell that is key to regulating the human immune system. The findings, published online in Nature on February 16, 2015, open the door to new research and development in drugs and personalized medicine to help those with autoimmune disorders such as inflammatory bowel disease or rheumatoid arthritis. The Nature paper was titled, “Super-Enhancers Delineate Disease-Associated Regulatory Nodes in T Cells.” The senior author of the Nature paper, John J. O'Shea, M.D., is the Scientific Director at NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The lead author, Golnaz Vahedi, Ph.D., is a post-doctoral fellow in Dr. O'Shea's lab in the Molecular Immunology and Inflammation Branch of the NIAMS. The study was performed in collaboration with investigators led by NIH Director Francis S. Collins, M.D., Ph.D., in the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI). Autoimmune diseases occur when the immune system mistakenly attacks its own cells, causing inflammation. Different tissues are affected in different diseases. For example, the joints become swollen and inflamed in rheumatoid arthritis, and the brain and spinal cord are damaged in multiple sclerosis. The causes of these diseases are not well understood, but scientists believe that they have a genetic component because they often run in families. "We now know more about the genetics of autoimmune diseases," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "Knowledge of the genetic risk factors helps us assess a person's susceptibility to disease. With further research on the associated biological mechanisms, it could eventually enable physicians to tailor treatments to each individual."
Prostate cancer is the second leading cause of cancer for men in the United States. Only one class of chemotherapy, called taxanes, is effective against the disease. A study published online on February 15, 2015 in Clinical Cancer Research, researchers have found that a newer member of the taxane family, called cabazitaxel, an FDA-approved drug, has properties that could make it more effective for some patients, a hypothesis currently being tested in clinical trials. Researchers also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel. The article was titled, “Novel Actions of Next-Generation Taxanes Benefit Advanced Stages of Prostate Cancer.” "It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they're both taxanes," says senior author Karen Knudsen, Ph.D., Interim Director of the Sidney Kimmel Cancer Center and a Professor of Cancer Biology at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia. It shows that we may not be taking full advantage of this next-generation taxane in the clinic." For years, docetaxel has been the only effective chemotherapy for men whose cancer was no longer responding to hormone treatments. The next-generation drug in the taxane family, cabazitaxel, was approved in 2010, but only for patients whose cancer no longer responded to hormone therapy or docetaxel treatment. Dr. Knudsen and colleagues explored how cabazitaxel worked, and demonstrated that it might be more effective sooner in treatment than docetaxel.
The pathological process amyloidosis, in which misfolded proteins (amyloids) form insoluble fibril deposits, occurs in many diseases, including Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2D). However, little is known about whether different forms of amyloid proteins interact or how amyloid formation begins in vivo. A new study published in The American Journal of Pathology has found evidence that amyloid from the brain can stimulate the growth of fibrils in the murine pancreas and pancreatic-related amyloid can be found along with brain-related amyloid in human brain senile plaques. Islet amyloid can be found in islets of Langerhans (photo) in almost all patients with T2D. Islet amyloid is made up of islet amyloid polypeptide (IAPP), which is derived from its precursor proIAPP. Accumulation of IAPP can lead to beta-cell death. In the brain, deposits of beta-amyloid in the cortex and blood vessels are characteristic findings in AD. Several clinical studies have shown that patients with T2D have almost a two-fold greater risk of developing AD. The data described in the current study suggest that one link between the two diseases may be the processes underlying amyloidosis. This investigation focused on understanding how amyloid deposits "seed" or spread within a tissue or from one organ to another. "Several soluble proteins are amyloid-forming in humans. Independent of protein origin, the fibrils produced are morphologically similar," said Gunilla T. Westermark, Ph.D, Department of Medical Cell Biology at Uppsala University in Sweden. "There is a potential for structures with amyloid-seeding ability to induce both homologous and heterologous fibril growth.
Penguins apparently can't enjoy or even detect the savory taste of the fish they eat or the sweet taste of fruit. A new analysis of the DNA evidence, which is described in in the February 16, 2015 issue of Current Biology, suggests that the flightless, waddling birds have lost three of the five basic tastes over evolutionary time. For them, it appears, food comes in only two flavors, salty and sour. The Current Biology article is entitled "Molecular Evidence for the Loss of Three Basic Tastes in Penguins." Many other birds, such as chickens and finches, can't taste sweet things either. But they do have receptors for detecting bitter and umami (or meaty) flavors. "Penguins eat fish, so you would guess that they need the umami receptor genes, but for some reason they don't have them," says Dr. Jianzhi "George" Zhang of the University of Michigan. "These findings are surprising and puzzling, and we do not have a good explanation for them. But we have a few ideas." It was Dr. Zhang's colleagues in China who led him to this discovery after they realized that they couldn't find some of the taste genes in their newly sequenced genomes of Adelie and emperor penguins. Dr. Zhang took a closer look at the penguin DNA to find that all penguin species lack functional genes for the receptors of sweet, umami, and bitter tastes. The researchers suggest that the genes encoding those taste receptors may have been lost in penguins not because they weren't useful, but rather because of the extremely cold environments in which penguins live. [Note: While some penguins have since moved to warmer climes, all penguins trace their roots to Antarctica.] Unlike receptors for sour and salty tastes, the taste receptors required for detecting sweet, umami, and bitter tastes are temperature-sensitive. They don't work when they get really cold anyway.
For decades, theories on the genetic advantage of sexual reproduction have been put forward, but none had ever been proven in humans, until now. Researchers at the University of Montreal and the Sainte-Justine University Hospital Research Centre in Montreal, Canada have just shown how humanity’s predispositions to disease gradually decrease the more we mix our genetic material together. This discovery was finally made possible by the availability in recent years of repositories of biological samples and genetic data from different populations around the globe. As humans procreate, generation after generation, the exchange of genetic material between man and woman causes our species to evolve, little by little. Chromosomes from the mother and the father recombine to create the chromosomes of their child. Scientists have known for some time, however, that the parents’ genomes don’t mix together in a uniform way. Chromosomes recombine frequently in some segments of the genome, while recombination is less frequent in others. These segments of low-frequency recombination will eventually recombine as other segments do, but it will take many, many generations. More specifically, the team of Canadian researchers, led by Dr. Philip Awadalla, discovered the following: the segments of the human genome that don’t recombine as often as others also tend to carry a significantly greater proportion of the more disease-enabling genetic mutations. [Mutations, also called “variations,” happen naturally and are not necessarily a cause for concern. They occur when genes get incorrectly copied from one parent to the child or after many generations’ exposure to certain environmental factors. Some mutations are benign, some beneficial. Bad mutations, however, can increase our risk of contracting or developing debilitating or life-threatening diseases.]
Researchers have discovered a novel role for Mitofusin 2, and the findings may point to a new treatment for patients with diseases caused by loss of the mitochondrial protein. The study appears in The Journal of Cell Biology . Mitofusin 2, and its closely related counterpart, Mitofusin 1, are located in the outer membrane of mitochondria. Both proteins are required for mitochondrial fusion, an important maintenance function in which adjacent organelles join together and exchange contents. Mice lacking the Mfn1 gene, which encodes Mitofusin 1, nevertheless seem perfectly healthy, but Mfn2-deficient mice die soon after birth. Moreover, mutations in theMfn2 gene are known to cause human diseases, including the peripheral neuropathy Charcot-Marie-Tooth type 2A. Lack of Mitofusin 2 therefore seems to affect mitochondrial function in other ways besides membrane fusion, but researchers have been unclear as to how. To find out, Max Planck Institute scientist Dr. Nils-Göran Larsson and colleagues investigated mouse heart muscle cells lacking Mfn2. They found that energy metabolism in these cells was impaired compared with that in healthy and Mfn1-deficient cells. They determined that the process was stalled because of reduced levels of coenzyme Q, a key component of the mitochondrial respiratory chain that generates cellular energy in the form of ATP. In the absence of Mitofusin 2, many of the enzymes and molecules involved in the pathway that generates precursors of coenzyme Q were decreased, indicating that Mitofusin 2 is required for coenzyme Q production. By supplementing Mfn2-deficient cells with coenzyme Q, Larsson and colleagues were able to partially restore respiratory chain function. They therefore think that coenzyme Q supplements might help treat patients with diseases caused by Mfn2 mutations.