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Archive - 2013

October 14th

New Giant Viruses Discovered, Possible Missing Link between Viruses and Cells

With the discovery of Mimivirus ten years ago and, more recently, Megavirus chilensis, researchers thought they had reached the farthest corners of the viral world in terms of size and genetic complexity. With a diameter in the region of a micrometer and a genome incorporating more than 1,100 genes, these giant viruses, which infect amoebas of the Acanthamoeba genus, had already largely encroached on areas previously thought to be the exclusive domain of bacteria. For the sake of comparison, common viruses such as the influenza or HIV viruses, only contain approximately ten genes each. In an article published in the July 19, 2013 issue of Science, the researchers from France and Sweden announced they had discovered two new giant viruses: Pandoravirus salinus, on the coast of Chile, and Pandoravirus dulcis, in a freshwater pond in Melbourne, Australia. Detailed analysis has shown that these first two Pandoraviruses have virtually nothing in common with previously characterized giant viruses. What's more, only a very small percentage (6%) of the proteins encoded by Pandoravirus salinus is similar to those already identified in other viruses or cellular organisms. With a genome of this size, Pandoravirus salinus demonstrates that viruses can be more complex than some eukaryotic cells. Another unusual feature of Pandoraviruses is that they have no gene allowing them to build a protein like the capsid protein, which is the basic building block of traditional viruses. Despite all these novel properties, Pandoraviruses display the essential characteristics of other viruses in that they contain no ribosomes, produce no energy, and do not divide.

October 10th

Badgers Responsible for 50% of TB in Cattle

Badgers are ultimately responsible for roughly half of tuberculosis (TB) in cattle in areas with high TB prevalence, according to new estimates. However, only approximately six per cent of infected cattle catch TB from badgers, with onward transmission between cattle herds accounting for the remainder of TB infections, the study suggests. The findings were published online on October 10, 2013 in the open-access journal PLOS Currents: Outbreaks. The role of badgers in spreading bovine TB has been debated intensely as part of discussions about whether badgers should be culled to control the disease. The Randomized Badger Culling Trial, which ran from 1998 to 2005, found evidence that culling could reduce TB in herds inside culled areas, while increasing TB in areas nearby. Mathematical models based on data from the trial were previously used to calculate an estimate of the proportion of TB in cattle that could ultimately be attributed to transmission from badgers. The new paper, by scientists at Imperial College London, provides a more detailed analysis. It estimates that badgers ultimately account for 52 per cent of cattle TB in areas where prevalence in cattle is high. There is considerable uncertainty around this estimate, but the authors say that 38 per cent is a robust minimum value for the estimate. There is no robust maximum value. Professor Christl Donnelly, from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London, said: “These findings confirm that badgers do play a large role in the spread of bovine TB.

Change in Circulating Tumor Cell Detection Has High Potential in the Prediction of Treatment Outcome in Prostate Cancer

A new study reveals that in the prediction of treatment outcome for castration-resistant prostate cancer, a change in circulating tumor cells detection might be more accurate than the change in prostate-specific antigen (PSA) levels. The findings of this award-winning study were presented at the recent EAU 13th Central European Meeting in Prague, Czech Republic (http://cem2013.uroweb.org/) October 4-6, 2013. "The research of the circulating tumor cells (CTC) is of utmost importance, because nowadays there is no reliable marker of both cancer-specific or overall survival in castration-resistant prostate cancer (CRPC) patients," explained the lead author of the study, Dr. Otakar Čapoun, of the Department of Urology at General Teaching Hospital Charles University in Prague, Czech Republic. "The goal of this study is to assess the possibility of the individualization of castration-resistant prostate cancer management. In cases with no favorable change in CTC detection during chemotherapy, the early switching to another therapy should be considered," commented Dr. Čapoun on the implications of the study, which was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic. Protocol of the grant project included the collection of peripheral blood from patients with metastatic CRPC prior to docetaxel therapy and after the fourth cycle of chemotherapy (CTX). Circulating tumor cells were detected by using a method of immunomagnetic separation. In the course of the study, multiplex PCR was performed after cytolysis of CTC and the expression of tumor-associated antigens (PSA, PSMA, and EGFR) was quantified. The methodology of the study was based on verbal evaluation, together with a report of the absolute values (ng/ml).

October 10th

How Microbes Can Survive Eons of Freezing Conditions

Most microbial researchers grow their cells in petri dishes to study how they respond to stress and damaging conditions. But, with the support of funding from NASA, researchers in Louisiana State University’s (LSU’s) Department of Biological Sciences tried something almost unheard of: studying microbial survival in ice to understand how microorganisms could survive in ancient permafrost, or perhaps even buried in ice on Mars. Dr. Brent Christner, associate professor of biological sciences, and colleagues at LSU including postdoctoral researcher Dr. Markus Dieser and Mary Lou Applewhite Professor John Battista, had results on DNA repair in ice-entrapped microbes published online on September 27, 2013 by the journal Applied and Environmental Microbiology. To understand how microbes survive in frozen conditions, Christner and colleagues focused on analysis of DNA, the hereditary molecule that encodes the genetic instructions used in the development and function of all organisms. “Microbes are made up of macromolecules that, even if frozen, are subject to decay,” Dr. Christner said. “We know of a range of spontaneous reactions that result in damage to DNA.” The worst kind of damage is known as a double-stranded break, where the microbe’s DNA is cleaved into two separate pieces that need to be put back together to make the chromosome functional. “This kind of damage is inevitable if cells exist frozen in permafrost for thousands of years and cannot make repairs,” Dr. Christner said. “Imagine that a microbe is in ice for extended periods of time and its DNA is progressively getting cut into pieces. There will eventually be a point when the microbe’s DNA becomes so damaged that it’s no longer a viable informational storage molecule. What is left is a corpse.” The situation would seem dire for the longevity of microbes in ice.

October 8th

“Zone in with Zon”—Nanomedicine Used to Target Breast Cancer Tumors

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated October 7, 2013, and published by TriLink BioTechnologies of San Diego, reviews some of the latest advances in breast cancer research in recognition of October as National Breast Cancer Awareness Month. Dr. Zon begins with an outline of some of the grim statistics about the deadly impact of breast cancer today and then goes on to describe existing treatments and a number of exciting and promising new therapeutic approaches that are being developed. Statistics from the NIH predict 232,340 new breast cancer cases and 39,620 deaths in 2013 in the U.S., Dr. Zon said. Nevertheless, in women diagnosed with breast cancer in the period of 1999 through 2006, the 5-year survival rate was 90%, which represents a significant improvement since the mid-1970s and is attributed to more screening and improved treatments. Among these treatments are tamoxifen and another selective estrogen receptor modulator (SERM), raloxifene, which have been approved by the FDA, and the monoclonal antibody trastuzumab, which is an accepted treatment for breast cancers that overproduce a protein called human epidermal growth factor receptor 2, or HER2. Dr. Zon also provided a description of cancer research expert Esther H. Chang, M.D., Ph.D., who has made significant achievements in specifically targeting tumors using antibody-fragment-tagged liposomal nanoparticles. Dr. Zon noted that Dr. Chang has referred to this process as involving “tiny little Fed Ex trucks.” Dr. Zon noted that tumor-targeted nanomedicine delivery of the p53 gene (SGT-53) has already successfully completed Phase I safety trials. He went on to note that nanomedicine researchers are currently seeking to develop a number of revolutionary tools.

2013 Chemistry Nobel Prize Awarded for Computer Modeling of Chemical Reactions

The Royal Swedish Academy of Sciences has decided, on October 9, 2013, to award the Nobel Prize in Chemistry for 2013 to Martin Karplus, Université de Strasbourg, France and Harvard University, Cambridge, MA, USA; Michael Levitt, Stanford University School of Medicine, Stanford, CA, USA; and Arieh Warshel, University of Southern California, Los Angeles, CA, USA “for the development of multiscale models for complex chemical systems.” Chemists once created models of molecules using plastic balls and sticks. Today, the modelling is carried out in computers. In the 1970s, Martin Karplus, Michael Levitt, and Arieh Warshel laid the foundation for the powerful programs that are used to understand and predict chemical processes. Computer models mirroring real life have become crucial for most advances made in chemistry today. Chemical reactions occur at lightning speed. In a fraction of a millisecond, electrons jump from one atomic nucleus to the other. Classical chemistry has a hard time keeping up; it is virtually impossible to experimentally map every little step in a chemical process. Aided by the methods now awarded with the Nobel Prize in Chemistry, scientists let computers unveil chemical processes, such as a catalyst’s purification of exhaust fumes or the photosynthesis in green leaves. The work of Karplus, Levitt, and Warshel is ground-breaking in that they managed to make Newton’s classical physics work side-by-side with the fundamentally different quantum physics. Previously, chemists had to choose to use one or the other. The strength of classical physics was that calculations were simple and could be used to model really large molecules. Its weakness was that it offered no way to simulate chemical reactions. For that purpose, chemists instead had to use quantum physics.

October 7th

2013 Medicine Nobel Prize Awarded for Discovery of Machinery Regulating Vesicular Traffic

The Nobel Assembly at Karolinska Institute in Sweden decided on October 7, 2013 to award the 2013 Nobel Prize in Physiology or Medicine jointly to James E. Rothman, Randy W.Schekman, and Thomas C. Südhof for their discoveries of the machinery regulating vesicle traffic, a major transport system in our cells. The 2013 Nobel Prize honours three scientists who have solved the mystery of how the cell organizes its transport system. Each cell is a factory that produces and exports molecules. For instance, insulin is manufactured and released into the blood and chemical signals called neurotransmitters are sent from one nerve cell to another. These molecules are transported around the cell in small packages called vesicles. The three Nobel Laureates have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell. Randy Schekman discovered a set of genes that were required for vesicle traffic. James Rothman unravelled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Thomas Südhof revealed how signals instruct vesicles to release their cargo with precision. Through their discoveries, Rothman, Schekman, and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders. In a large and busy port, systems are required to ensure that the correct cargo is shipped to the correct destination at the right time.

October 6th

Gene Activity and Transcript Patterns Visualized for First Time in Thousands of Single Cells

Biologists of the University of Zurich have developed a method to visualize the activity of genes in single cells. The method is so efficient that, for the first time, a thousand genes can be studied in parallel in ten thousand single human cells. Applications lie in fields of basic research and medical diagnostics. The new method shows that the activity of genes and the spatial organization of the resulting transcript molecules, strongly vary between single cells. Whenever cells activate a gene, they produce gene-specific transcript molecules, which make the function of the gene available to the cell. The measurement of gene activity is a routine activity in medical diagnostics, especially in cancer medicine. Today's technologies determine the activity of genes by measuring the amount of transcript molecules. However, these technologies can neither measure the amount of transcript molecules of one thousand genes in ten thousand single cells, nor the spatial organization of transcript molecules within a single cell. The fully automated procedure, developed by biologists of the University of Zurich under the supervision of Professor Lucas Pelkmans, allows, for the first time, a parallel measurement of the amount and spatial organization of single transcript molecules in ten thousands single cells. The results, which were published online on October 6, 2013 in Nature Methods, provide completely novel insights into the variability of gene activity of single cells. The method developed by Dr. Pelkmans' Ph.D. students Nico Battich and Thomas Stoeger is based upon the combination of robots, an automated fluorescence microscope, and a supercomputer. "When genes become active, specific transcript molecules are produced. We can stain them with the help of a robot," explains Stoeger.

October 3rd

Toxoplasma Infection of Mice May Permanently Eliminate Their Fear of Cats

The toxoplasma parasite can be deadly, causing spontaneous abortion in pregnant women or killing immune-compromised patients, but it has even stranger effects in mice. Infected mice lose their fear of cats, which is good for both cats and the parasite, because the cat gets an easy meal and the parasite gets into the cat’s intestinal tract, the only place it can sexually reproduce and continue its cycle of infection. New research by graduate student Wendy Ingram at the University of California, Berkeley, reveals a scary twist to this scenario: the parasite’s effect seem to be permanent. The fearless behavior in mice persists long after the mouse recovers from the flu-like symptoms of toxoplasmosis, and for months after the parasitic infection is cleared from the body, according to research published today online on September 18, 2013 in the open-accessjournal PLOS ONE. “Even when the parasite is cleared and it’s no longer in the brains of the animals, some kind of permanent long-term behavior change has occurred, even though we don’t know what the actual mechanism is,” Ingram said. She speculated that the parasite could damage the smell center of the brain so that the odor of cat urine can’t be detected. The parasite could also directly alter neurons involved in memory and learning, or it could trigger a damaging host response, as in many human autoimmune diseases. Ingram became interested in the protozoan parasite, Toxoplasma gondii, after reading about its behavior-altering effects in mice and rats and possible implications for its common host, the domesticated cat, and even humans. One third of people around the world have been infected with toxoplasma and probably have dormant cysts in their brains.

September 26th

New Dwarfism Mutation Identified in Dogs; Also Candidate for Human Dwarfism

Professor Hannes Lohi’s research group at the University of Helsinki and Folkhälsan Research Center in Finland has identified a mutation in the ITGA10 gene that causes chondrodysplasia (dwarfism) in two dog breeds, the Norwegian Elkhound and the Karelian Bear Dog. The research revealed a new chondrodysplasia gene in dogs, and a candidate gene for human chondrodysplasias. The finding has implications on bone biology as well as canine health. A genetic test can now be used to identify mutation carriers in the two affected dog breeds. The study was published online in the open-access journal PLOS ONE on 25 September 2013. The ITGA10 mutation causes autosomal recessive disproportionate short-stature dwarfism of varying severity. The appearance of affected dogs is characterized by considerably shorter limbs than normal dogs, and other skeletal abnormalities may follow, including bowed forearms, abnormal digits, and malformed femoral heads. The ITGA10 gene codes for an integrin subunit that assembles into a cartilage-specific collagen receptor, found in the growth plates of long bones. The receptor is important for the process of endochondral ossification, in which the cartilage cells first proliferate, and are then replaced by bone tissue. Accordingly, several abnormalities have been found in the growth plates of affected dogs both in radiographic and histological examinations. The causative mutation was mapped to a specific region on canine chromosome 17 by comparing the genomes of affected and healthy dogs. Further analysis of this chromosomal region revealed a single nucleotide change in the ITGA10 gene, which disrupts the gene by introducing a signal that prematurely ends the production of the encoded integrin subunit.